The Autism Genome Project

Lead Research Organisation: University of Oxford
Department Name: Wellcome Trust Centre for Human Genetics

Abstract

Autism Spectrum Disorders are severe neurodevelopmental disorders, with a prevalence of ~60 in 10000, characterised by impairments in verbal and non-verbal communication, processing social and emotional information and repetitive or stereotyped behaviours. The cause of autism is unknown but there is strong evidence for the involvement of inherited genetic factors. The Autism Genome Project (AGP) proposes to tease apart the complex genetic etiology of autism. The AGP brings together leading experts in autism research from 13 groups in Europe and North America, with expertise in the autism phenotype, statistical genetic analysis, and high-throughput methods of gene discovery. To achieve our goals, the AGP has a powerful resource of 1,496 multiplex families (two or more affected individuals in a family) and ~2,000 trios (one affected individual and both parents). The multiplex family samples have been genotyped and analysed for linkage using a set of 10000 single nucleotide polymorphisms (SNPs) spread across the genome. Analysis of the SNP data using a qualitative autism diagnosis has identified regions on chromosomes 2q, 5p, 7q, 9p, and 11p that likely harbour variants increasing susceptibility to autism.

Our study design will take four parallel, complementary approaches to identify autism susceptibility genes. We will integrate these approaches in a staged design of experiments that maximises our chance of success while being cost effective. We will (1) follow-up our top four-five regions of linkage (2) use the richness of the autism phenotype to help us understand how genetics and different aspects of the clinical picture are related (3) search for changes in copy number (deletions and duplications) throughout the genome that may also be causative for autism and (4) analyse candidate genes for mutations and association with autism. Variants in genes emerging from linkage and fine-mapping, copy number analysis, and data from outside sources will be evaluated in the second and third years of the project through our staged experimental design. The large cohort of AGP trio families will be used as an independent sample for validation of significant findings obtained in the multiplex families. Identifying susceptibility alleles and a proper understanding of the underlying genetic and molecular mechanisms will be key to identifying any interacting environmental factors, and for developing rational preventative and treatment strategies to improve quality of life.

Technical Summary

Autism Spectrum Disorders (ASDs) are lifelong neurodevelopmental diseases affecting about 0.6% of the population with significant economic, health and well-being costs to society and families involved. Twin and family studies point to a strong genetic predisposition involving epistatic interactions between multiple loci. The behavioural phenotype is variable and extends beyond ASDs to include social, communication and repetitive/restricted behavioural abnormalities, alone or in combination, in relatives of normal intelligence. Identifying susceptibility genes will be important for understanding the neurodevelopmental pathways involved, identifying putative environmental factors and for developing specific preventative and treatment strategies. To identify susceptibility genes, the Autism Genome Project (AGP) was initiated to pool resources, and clinical and scientific expertise from four separate consortia involving 13 North American and European sites. The AGP has a large and rich phenotypic data set on multiplex (1496) and trio (2000) families so that specific statistical and genetic approaches can be brought to bear in the search for susceptibility loci and their relationship with phenotypic expression. The AGP has recently completed a 10K SNP-based genome scan for linkage and has provided support for linkage on chromosomes 2q, 5p, 7q, 9p and 11p. We hypothesize that liability to autism is due to rare and more common genetic variation, and that inheritance of multiple combinations of genetic variants result in this disorder.

Our study design will take four parallel, complementary approaches to identify autism susceptibility genes. Each approach will be integrated in an experimental staged design to maximise power and minimise costs. (1) High-density SNP genotyping of the four-five principal regions of linkage from the AGP genome scan will be performed to search for association. (2) Refinement of the autism phenotype will identify auxiliary traits for use in detailed analyses to identify loci that influence expression of autism-related traits. (3) Copy Number Variations (CNVs) identified from dense genotype data will be analysed in the autism sample and a control sample as there is now strong evidence that liability to autism in some individuals is linked to genomic instability. (4) Compelling candidate genes, especially those with prior evidence, functional rationale for involvement in autism and those located in regions of moderate linkage will be evaluated for association to autism. Subsequently, candidate genes emerging from these approaches will be evaluated in a large cohort of AGP trio families in the second and third years of the project through our staged experimental design.
 
Description MRC Program Grant (Gene-gene and gene-environment interactions underlying speech, language and reading development)
Amount £169,775 (GBP)
Funding ID G0800523 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2008 
End 12/2010
 
Description NLM Foundation Programme grant
Amount £759,921 (GBP)
Organisation Nancy Lurie Marks (NLM) Family Foundation 
Sector Charity/Non Profit
Country United States
Start 10/2006 
End 09/2010
 
Description Simons Foundation Programme grant
Amount £759,921 (GBP)
Organisation Simons Foundation 
Sector Charity/Non Profit
Country United States
Start 10/2006 
End 09/2010
 
Description AGP Consortium 
Organisation Children's Hospital of Philadelphia
Country United States 
Sector Hospitals 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation German Cancer Research Center
Country Germany 
Sector Public 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation German Cancer Research Center
Country Germany 
Sector Public 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Goethe University Frankfurt
Country Germany 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Icahn School of Medicine at Mount Sinai
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Indiana University
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation McMaster University
Country Canada 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation National Institute of Health and Medical Research (INSERM)
Department INSERM U952 (Pathophysiology of central nervous system diseases)
Country France 
Sector Public 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Nationwide Children's Hospital
Department Battelle Center for Mathematical Medicine
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Stanford University
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Stella Maris Institute for Child and Adolescent Neuropsychiatry
Country Italy 
Sector Hospitals 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Trinity College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University College Dublin
Country Ireland 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Bologna
Country Italy 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of California, Los Angeles (UCLA)
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Illinois
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Miami
Department John P. Hussman Institute for Human Genomics
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of North Carolina at Chapel Hill
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Pennsylvania
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Pennsylvania
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Pittsburgh
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Toronto
Country Canada 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Utah
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation University of Washington
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description AGP Consortium 
Organisation Vanderbilt University
Country United States 
Sector Academic/University 
PI Contribution The Autism Genome Project (AGP) is a large-scale genetics research project, bringing together researchers from over 50 centres across Europe, the USA and Canada (main sites listed in 2.5). [Website: www.autismgenome.org] There have been two AGP projcts: Phase 1 (2004-2007) and Phase 2 (2007-2010; budget $16m). The main Phase 2 funders are: Autism Speaks, USA ($5.3m), the MRC ($1.5m), Genome Canada ($1.3m), HRB Ireland ($8m), and the Hilibrand Foundation, USA ($1m). Prof. Monaco is a leading PI on the AGP. He heads the current Phase 2 project. The Monaco Research Group (Oxford University) has actively contributed to both projects, and collaborated closely with all AGP sites. All work was funded by the MRC. Main contributions of the Monaco Group include: contribution of samples (simplex and multiplex families from the IMGSAC Consortium - see below), genotyping (1M Illumina platform), sequencing, candidate gene studies, GWAS and CNV analyses, and analyses of phenotypic data. In addition, the AGP Project Manager is in the Monaco Group.
Collaborator Contribution See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8See 2.6/2.8
Impact 1) AGP Phase 1 (finalised in 2007): Main publications (all listed in section 2): PMIDs 17322880; 18632090. In Phase 1, the AGP achieved its initial goal of assembling the world's largest gene bank for autism. This was the most comprehensive database of autism families at the time, including both multiplex and simplex families. The AGP also achieved its goal of carrying out the world's most comprehensive genome scan into the genetics of autism (total 1,400 families). Some main findings from the GWAS and CNV analyses conducted: Evidence was found for linkage in 11p12-p13 (not previously a major focus for discovery of autism risk loci), as well as regions 5p and 9p. CNV analyses supported accumulating evidence for a role for neurexins and neuroligins in ASDs. 2) AGP Phase 2 (ongoing): Note: a detailed Year 2 progress report and financial report was submitted to the MRC (Gavin Malloch) in April 2009. A final report will be submitted in April 2010. A) 1M genotyping: In Phase 2, the AGP aims to identify the rare genetic variants that are associated with ASDs, including copy number variations (CNVs). Over 3,000 new trios (from multiplex and simplex autism families) will be genotyped on the 1M Illumina platform. Genotyping has already been finalised for half this sample, and GWAS and CNV analyses conducted. Two main Phase 2 papers have resulted to date, investigating copy number variations and association at a genome-wide level (PMID: 20531469; 20663923). Ahead of this main publications, the Monaco Group has also published a paper highlighting three specific CNVs of interest to psychiatric geneticists (15q13.3, 16p11.2 and 22q11.2), found in IMGSAC families genotyped as part of the Phase 2 project: "Chromosomal Copy Number Variation in Psychiatric Disorders", A. Pagnamenta and A. Monaco, European Psychiatric Review, 2009, 2(1): 8-12, (PMID pending). Genotyping of the remainder of the Phase 2 sample will be finalised by end 2009. GWAS and CNV analyses of the complete sample (>3,000 trios) will be completed in 2010. It is anticipated that this will result in a second main AGP Phase 2 publication. B) Phenotyic data analyses: In Phase 2, detailed phenotypic data are also being uploaded for the complete AGP sample set (over 7,500 families). This includes: ADI, ADOS, IQ, Vinelands, Body Measurements and Family Type data. (Later, SRS and RBS will also be added). A number of analyses are currently being conducted by collabortions of AGP sites, on these rich - and growing - phenotypic datasets. It is anticipated that at least five AGP publications will result from this work in 2010. C) John Hopkins / BROAD collaboration: In Phase 2, the AGP also collaborated with Johns Hopkins on a new autism study. The AGP carried out a replication study for main findings from this study, and is acknowledged in the main study publication: PMID: 19812673. 3) Phase 3 project (planned): The AGP is currently seeking funding for a third project (Phase 3), to start in 2010: Prof Monaco has submitted a draft grant appliction, together with Newcastle University, to the MRC (Gavin Malloch), which focuses on translational genetics: "Translating Autism Genetic Research into Clinical Practice: Investigating the clinical utility of increased molecular genetic testing for children with ASD". (Total budget requested: £1.37). It is likely that Autism Speaks (USA) will provide funding for core AGP activities in 2010 (~$600k), with further funding potentially available in 2011. The AGP will seek NIH funding for CIDR to genotype approx. 2,000 additional trios on the 1M Illumina platform in 2010. Additional funding will also be sought from other funders, including Genome Canada and HRB Ireland.
 
Description Conference, Ormskirk 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact Approximately 100 individuals, comprising parents, teachers and health workers involved in autism spectrum disorders, attended a talk on the autism genetics work performed in the Monaco laboratory. This resulted in an active question and answer session at the end of the presentation.

Increased interest in the genetics of autism spectrum disorders among participants.
Year(s) Of Engagement Activity 2008
 
Description Media interviews (including BBC) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Media (as a channel to the public)
Results and Impact In October 2009, two AGP papers were published, to which the Monaco Group had strongly contributed: "Chromosomal Copy Number Variation in Psychiatric Disorders, Pagnamenta, A and Monaco, A, European Psychiatric" Review 2009 2(1): 8-12 (PMID pending); and "A genome-wide linkage and association scan reveals novel loci for autism", Weiss L.A., Arking D.E., the Gene Discovery Project of Johns Hopkins, the Autism Consortium, Daly M.J., Nature 461, 802-808. (PMID: 19812673). Prof Monaco and Dr Pagnamenta were interviewed on BBC national news (News 24)and local radio, to explain the findings from these papers, and what they meant for patients and people with autism.

Broad media coverage and dissemination of information on AGP findings on autism [More here: http://www.autismgenome.org/news/index.htm]
Year(s) Of Engagement Activity 2009
URL http://www.autismgenome.org/news/index.htm
 
Description Media interviews (including BBC) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Media (as a channel to the public)
Results and Impact Information was disseminated nationwide via multiple media outlets, including the BBC news website, in response to an AGP Phase 2 paper investigating copy number variation in autism (PMID 20531469).

Broad media coverage and dissemination of information on AGP findings on autism [More here: http://www.autismgenome.org/news/index.htm]
Year(s) Of Engagement Activity 2010
URL http://www.autismgenome.org/news/index.htm
 
Description UN Presentation 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Policymakers/politicians
Results and Impact 2nd April 2008: World Autism Day: To celebrate the first ever United Nations (UN) sanctioned World Autism Awareness Day, the UN held a Panel Discussion on autism. The event was sponsored by the Government of the State of Qatar in collaboration with the World Health Organization and Autism Speaks USA. Prof Monaco was one of the international group of speakers to discuss the global aspect of autism. In his presentation he referred to the ongoing work of the AGP. [Further details here: http://www.autismgenome.org/news/index.htm] In parallel to this event, during the Second Annual International Forum for Children with Special Needs held in Doha, Autism Speaks and Qatar's Shaffalah Centre, which assists disabled children, announced plans to launch an Autism Speaks Programme in Qatar.

Raising awareness of autism at the interntional level. The AGP has initiated a collaboration with Qatar's Shaffalah Centre, to recruit over 150 families with autism in Qatar (50 collected to date), and to genotype DNA samples from these families on the 1M Illumina platform. Subsequently, it is anticipated that the Centre would become a full AGP member in late 2010.
Year(s) Of Engagement Activity 2008,2009