Translating genome-wide association data from the WTCCC study into biological and clinical insights in type 2 diabetes
Lead Research Organisation:
University of Oxford
Department Name: RDM OCDEM
Abstract
Diabetes is a major and growing cause of disease and death in the UK and beyond. Most diabetes arising after early adulthood is due to ?type 2 diabetes?: almost 10 percent of the world?s population either has this condition or will develop it during their lifetime. Despite this global importance, understanding of the processes which lead to development of type 2 diabetes is far from complete, and much needs to be done to develop more effective approaches to prevention and treatment.
One of the most promising routes to a better understanding of diabetes comes from identifying the genes which influence an individual?s predisposition to develop the disease. In recent years, there have been some promising developments and several such genes have been identified. More recently, through advances in knowledge and technology that have followed the sequencing of the human genome, it has become possible to search for such genes in a systematic and ?genomewide? fashion. The applicants on this proposal are currently completing such a ?genomewide association? study (the largest yet conducted into the genetics of diabetes). Analysis of the experimental data will commence shortly and will provide initial clues to the locations of many novel diabetes genes. However, a great deal of work will still be required to separate real effects from spurious findings due to chance or error, and to establish beyond doubt the identities of the genes involved. This work, which involves studying a further 50,000 DNA samples, occupies the first part of our research proposal.
With such a set of confirmed diabetes-susceptibility signals in hand, we aim to translate these discoveries into an improved understanding of the biology of diabetes. We will do this in various ways: for instance, by studying how these genes interact with environmental factors (poor diet, lack of exercise) to influence risk of diabetes. Finally, we want to see whether it is practical to use this genetic information to improve the treatment and prevention of diabetes. We will ask whether the genetic differences we have identified will allow us to predict how likely it is that a given individual will develop diabetes and which treatments may be particularly beneficial.
The work will be performed by groups in Oxford, Exeter and Dundee who have spent the last decade working together to understand the causes of type 2 diabetes. The funding requested will enable them to make major strides towards this goal.
One of the most promising routes to a better understanding of diabetes comes from identifying the genes which influence an individual?s predisposition to develop the disease. In recent years, there have been some promising developments and several such genes have been identified. More recently, through advances in knowledge and technology that have followed the sequencing of the human genome, it has become possible to search for such genes in a systematic and ?genomewide? fashion. The applicants on this proposal are currently completing such a ?genomewide association? study (the largest yet conducted into the genetics of diabetes). Analysis of the experimental data will commence shortly and will provide initial clues to the locations of many novel diabetes genes. However, a great deal of work will still be required to separate real effects from spurious findings due to chance or error, and to establish beyond doubt the identities of the genes involved. This work, which involves studying a further 50,000 DNA samples, occupies the first part of our research proposal.
With such a set of confirmed diabetes-susceptibility signals in hand, we aim to translate these discoveries into an improved understanding of the biology of diabetes. We will do this in various ways: for instance, by studying how these genes interact with environmental factors (poor diet, lack of exercise) to influence risk of diabetes. Finally, we want to see whether it is practical to use this genetic information to improve the treatment and prevention of diabetes. We will ask whether the genetic differences we have identified will allow us to predict how likely it is that a given individual will develop diabetes and which treatments may be particularly beneficial.
The work will be performed by groups in Oxford, Exeter and Dundee who have spent the last decade working together to understand the causes of type 2 diabetes. The funding requested will enable them to make major strides towards this goal.
Technical Summary
Recent advances in the understanding of human genome sequence variation, allied to advances in genotyping technology and availability of large well-characterized clinical samples have reinvigorated efforts to identify the variants influencing susceptibility to type 2 diabetes (T2D). The Wellcome Trust Case Control Consortium is the largest genome-wide association study currently in progress worldwide and genotyping of 2000 T2D cases and 3000 UK controls on the 500k Affymetrix platform will be complete by October 2006. The current proposal outlines our plans to follow-up the findings of this unprecedented study of T2D genetics using the extensive clinical resources available to the applicants and their collaborators. We plan to:
(a) perform extensive validation and replication studies to ensure robust identification of the principal common T2D-susceptibility SNPs against the background of type 1 error and undetected bias. Key to this exercise are plans for combined analysis of all available dense-map T2D genome-wide association data (~5500 cases, 6500 controls from 4 groups) in early 2007 through the IGWANA consortium. We will take the 1500 variants with the most compelling association signals from this combined analysis through successive rounds of validation and replication involving up to 50,000 samples. As we show, this design provides excellent power to retrieve the majority of common SNP-based variants with modest or large T2D-susceptibility effects with negligibly low false positive report probabilities;
(b) identify the variants driving each association signal (through fine-mapping, resequencing, and assays of copy number variation);
(c) translate these findings into insights into the epidemiology, physiology, genetic architecture and biology of T2D, in studies of over 100,000 samples available to the applicants and their collaborators;
(d) evaluate the potential for the application of the findings to the clinical management of diabetes. A key resource will be the Wellcome-Trust-funded Dundee-based UK Type 2 Diabetes Genetics Consortium Case-Control Collection which provides substantial health-related outcome data on over 7000 diabetic cases within the UK?s most-advanced record linkage system.
The applicants have a strong track-record in the successful implementation of large-scale genetic studies. They have pioneered large-scale association studies in T2D, have responsibility for the T2D component of the WTCCC and are playing a leading role in several major international genetics consortia. They are uniquely-placed to deliver insights into the pathogenesis of T2D, and to initiate the task of translating those findings into advances in clinical care.
(a) perform extensive validation and replication studies to ensure robust identification of the principal common T2D-susceptibility SNPs against the background of type 1 error and undetected bias. Key to this exercise are plans for combined analysis of all available dense-map T2D genome-wide association data (~5500 cases, 6500 controls from 4 groups) in early 2007 through the IGWANA consortium. We will take the 1500 variants with the most compelling association signals from this combined analysis through successive rounds of validation and replication involving up to 50,000 samples. As we show, this design provides excellent power to retrieve the majority of common SNP-based variants with modest or large T2D-susceptibility effects with negligibly low false positive report probabilities;
(b) identify the variants driving each association signal (through fine-mapping, resequencing, and assays of copy number variation);
(c) translate these findings into insights into the epidemiology, physiology, genetic architecture and biology of T2D, in studies of over 100,000 samples available to the applicants and their collaborators;
(d) evaluate the potential for the application of the findings to the clinical management of diabetes. A key resource will be the Wellcome-Trust-funded Dundee-based UK Type 2 Diabetes Genetics Consortium Case-Control Collection which provides substantial health-related outcome data on over 7000 diabetic cases within the UK?s most-advanced record linkage system.
The applicants have a strong track-record in the successful implementation of large-scale genetic studies. They have pioneered large-scale association studies in T2D, have responsibility for the T2D component of the WTCCC and are playing a leading role in several major international genetics consortia. They are uniquely-placed to deliver insights into the pathogenesis of T2D, and to initiate the task of translating those findings into advances in clinical care.
Organisations
- University of Oxford, United Kingdom (Lead Research Organisation)
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (Collaboration)
- University of Cape Town (Collaboration)
- University of KwaZulu-Natal (Collaboration)
- Lausanne University, Switzerland (Collaboration)
- Boehringer Ingelheim, Germany (Collaboration)
- University of Dundee, United Kingdom (Collaboration)
- University of California Los Angeles, United States (Collaboration)
- Helmholtz Association of German Research Centres (Collaboration)
- Harvard University (Collaboration)
- Institute of Cancer Research UK (Collaboration)
- King's College Hospital Charitable Trust, United Kingdom (Collaboration)
- International Diabetes Institute (Collaboration)
- AstraZeneca plc (Collaboration)
- University of Pennsylvania, United States (Collaboration)
- Stanford University, United States (Collaboration)
- F. Hoffmann-La Roche AG (Collaboration)
- deCODE Genetics (Collaboration)
- Sanofi (Collaboration)
- University of Melbourne, Australia (Collaboration)
- Servier Laboratories (Collaboration)
- Center for Human Genetic Research; Broad Institute (Collaboration)
- Eli Lilly & Company Ltd (Collaboration)
- University of Bristol, United Kingdom (Collaboration)
- Imperial College London, United Kingdom (Collaboration)
- GlaxoSmithKline (GSK) (Collaboration)
- The Wellcome Trust Sanger Institute (Collaboration)
- University of Cambridge, United Kingdom (Collaboration)
- Broad Institute (Collaboration)
- University of Geneva, Switzerland (Collaboration)
- University of Exeter, United Kingdom (Collaboration)
- University of Michigan, United States (Collaboration)
- McGill University, Canada (Collaboration)
- University of Chicago, United States (Collaboration)
- Pfizer Ltd (Collaboration)
- Lund University (Collaboration)
- Erasmus MC (Collaboration)
- Novo Nordisk (Collaboration)
Publications
't Hart LM
(2013)
The CTRB1/2 locus affects diabetes susceptibility and treatment via the incretin pathway.
in Diabetes
Berndt SI
(2013)
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture.
in Nature genetics
CARDIoGRAMplusC4D Consortium
(2013)
Large-scale association analysis identifies new risk loci for coronary artery disease.
in Nature genetics
Chen J
(2019)
Genome-wide association study of type 2 diabetes in Africa.
in Diabetologia
Costelloe SJ
(2012)
Gene-targeted analysis of copy number variants identifies 3 novel associations with coronary heart disease traits.
in Circulation. Cardiovascular genetics
DIAbetes Genetics Replication And Meta-Analysis (DIAGRAM) Consortium
(2014)
Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.
in Nature genetics
Donnelly LA
(2013)
Robust association of the LPA locus with low-density lipoprotein cholesterol lowering response to statin treatment in a meta-analysis of 30 467 individuals from both randomized control trials and observational studies and association with coronary artery disease outcome during statin treatment.
in Pharmacogenetics and genomics
Donnelly LA
(2011)
Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study.
in Clinical pharmacology and therapeutics
Dupuis J
(2010)
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
in Nature genetics
| Description | Chief Medical Officers Genomics Advisory Committee |
| Geographic Reach | National |
| Policy Influence Type | Participation in a advisory committee |
| Description | Genome Quebec Advisory Board |
| Geographic Reach | North America |
| Policy Influence Type | Participation in a advisory committee |
| Description | House of Lords Enquiry into genetic Medicine |
| Geographic Reach | National |
| Policy Influence Type | Gave evidence to a government review |
| Description | Human Genetics Commission |
| Geographic Reach | National |
| Policy Influence Type | Participation in a national consultation |
| Description | NIH Target Validation Committee (Diabetes) |
| Geographic Reach | North America |
| Policy Influence Type | Participation in a national consultation |
| Impact | Designing private-public partnership between NIH and pharma to develop Target Validation Consortium |
| Description | Topol Review into NHS WOrkforce Strategy (Co-Chair Genomics Panel) |
| Geographic Reach | National |
| Policy Influence Type | Gave evidence to a government review |
| Description | extensive citation of our work in clinical reviews |
| Geographic Reach | Multiple continents/international |
| Policy Influence Type | Citation in clinical reviews |
| Description | CEED3 Collaborative European effort to develop diabetes diagnostics (3m euros across 12 participants) |
| Amount | £205,000 (GBP) |
| Funding ID | 223211 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 01/2008 |
| End | 12/2012 |
| Description | Diabetes UK project grant |
| Amount | £142,000 (GBP) |
| Organisation | Diabetes UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 02/2008 |
| End | 01/2010 |
| Description | Diabetes UK, Clinical Training Fellowship |
| Amount | £129,000 (GBP) |
| Organisation | Diabetes UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2008 |
| End | 01/2010 |
| Description | Diabetes UK, Project Grant |
| Amount | £178,000 (GBP) |
| Organisation | Diabetes UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2009 |
| End | 12/2010 |
| Description | Diabetes UK, Project Grant Using human genetics to understand the role of adiponectin in type 2 diabetes and insulin resistance. |
| Amount | £214,000 (GBP) |
| Funding ID | 12/0004470 |
| Organisation | Diabetes UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2009 |
| End | 09/2012 |
| Description | Diabetes and Wellness Foundation fellowship for Jessica Tyrrell |
| Amount | £172,389 (GBP) |
| Organisation | The Diabetes Research & Wellness Foundation |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2015 |
| End | 12/2017 |
| Description | ENGAGE European network for genetic and genomic epidemiology (12m euros across 26 participants) |
| Amount | £378,462 (GBP) |
| Funding ID | 201413 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 01/2008 |
| End | 12/2012 |
| Description | EPI-MIGRANT Identification of epigenetic markers underlying increased risk of T2D in South Asians (3m euros across 12 participants) |
| Amount | £217,000 (GBP) |
| Funding ID | 279143 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 01/2012 |
| End | 12/2014 |
| Description | EU Innovative Medicines Initiative DIRECT project (40m euros across 20 participants) |
| Amount | £1,600,000 (GBP) |
| Funding ID | 115317 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 01/2012 |
| End | 12/2018 |
| Description | Grand opportunity grants |
| Amount | £14,000,000 (GBP) |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 10/2009 |
| End | 09/2012 |
| Description | Henry Wellcome Fellowships |
| Amount | £250,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2008 |
| End | 06/2012 |
| Description | Innovative Medicines Initiative (StemBANCC) |
| Amount | € 53,000,000 (EUR) |
| Funding ID | 115439 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 10/2012 |
| End | 09/2018 |
| Description | Innovative Medicines Initiative BEATDKD |
| Amount | € 15,000,000 (EUR) |
| Funding ID | BEATDKD |
| Organisation | European Commission |
| Department | Innovative Medicines Initiative (IMI) |
| Sector | Public |
| Country | Belgium |
| Start | 09/2017 |
| End | 08/2022 |
| Description | Innovative Medicines Initiative RHAPSODY |
| Amount | € 8,000,000 (EUR) |
| Funding ID | 115881 |
| Organisation | European Commission |
| Department | Innovative Medicines Initiative (IMI) |
| Sector | Public |
| Country | Belgium |
| Start | 04/2016 |
| End | 03/2020 |
| Description | JDRF Special Award |
| Amount | $400,000 (USD) |
| Organisation | Juvenile Diabetes Research Foundation (JDRF) |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2014 |
| End | 10/2015 |
| Description | MRC CASE |
| Amount | £98,000 (GBP) |
| Funding ID | MR/P016065/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2017 |
| End | 08/2021 |
| Description | MRC Clinical Training Fellowship |
| Amount | £212,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2008 |
| End | 01/2011 |
| Description | MRC Project Grant |
| Amount | £502,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2014 |
| End | 08/2018 |
| Description | MRC Project Grant (KlF14) |
| Amount | £700,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 09/2012 |
| End | 02/2015 |
| Description | MRC Using genetics to understand sleep and chronotype and their relationship to obesity and type 2 diabetes. |
| Amount | £401,000 (GBP) |
| Funding ID | MR/P012167/1 |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2017 |
| End | 01/2019 |
| Description | NIH R01 |
| Amount | $2,400,000 (USD) |
| Funding ID | DK098032 |
| Organisation | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 09/2012 |
| End | 08/2016 |
| Description | NIH R01 |
| Amount | $1,900,000 (USD) |
| Funding ID | MH101814 |
| Organisation | National Institutes of Health (NIH) |
| Department | National Institute of Mental Health (NIMH) |
| Sector | Public |
| Country | United States |
| Start | 09/2013 |
| End | 08/2016 |
| Description | NovoNordisk Funden Immunometabolism |
| Amount | kr 12,000,000 (DKK) |
| Funding ID | TRiiC |
| Organisation | Novo Nordisk Foundation |
| Sector | Charity/Non Profit |
| Country | Denmark |
| Start | 05/2016 |
| End | 04/2020 |
| Description | Program grant |
| Amount | £1,700,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 02/2015 |
| End | 01/2018 |
| Description | Project Grant |
| Amount | £129,000 (GBP) |
| Organisation | Diabetes UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2010 |
| End | 02/2012 |
| Description | SUMMIT SUrrogate markers for Micro- and Macro-vascular hard endpoints for Innovative diabetes Tools (28.4m euros across 23 participants) |
| Amount | £400,000 (GBP) |
| Funding ID | 115006 |
| Organisation | European Commission |
| Sector | Public |
| Country | European Union (EU) |
| Start | 11/2009 |
| End | 10/2015 |
| Description | Studentship |
| Amount | £72,000 (GBP) |
| Organisation | Diabetes UK |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2010 |
| End | 12/2013 |
| Description | U01 |
| Amount | $1,800,000 (USD) |
| Funding ID | DK105535 |
| Organisation | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
| Sector | Charity/Non Profit |
| Country | United States |
| Start | 04/2015 |
| End | 03/2019 |
| Description | U01 award |
| Amount | £1,500,000 (GBP) |
| Organisation | National Institutes of Health (NIH) |
| Sector | Public |
| Country | United States |
| Start | 09/2009 |
| End | 07/2015 |
| Description | Wellcome Career Development Fellowship |
| Amount | £791,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 04/2009 |
| End | 03/2015 |
| Description | Wellcome Investigator Award |
| Amount | £2,250,000 (GBP) |
| Funding ID | 212259/Z/18/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 11/2018 |
| End | 10/2024 |
| Description | Wellcome Strategic Award |
| Amount | £16,006,928 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2008 |
| End | 05/2011 |
| Description | Wellcome Strategic Award (Next-Generation Disease Association Analyses: Low pass Sequencing and High Density SNP genotyping for type 2 diabetes) |
| Amount | £2,592,923 (GBP) |
| Funding ID | 090367 |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2009 |
| End | 06/2013 |
| Description | Wellcome Trust Henry Dale award to Rachel Freathy |
| Amount | £800,000 (GBP) |
| Funding ID | 104150/Z/14/Z |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 01/2015 |
| End | 01/2021 |
| Description | Wellcome Trust Project GRant |
| Amount | £868,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 06/2008 |
| End | 05/2012 |
| Description | Wellcome Trust Project Grant |
| Amount | £440,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 09/2008 |
| End | 07/2011 |
| Description | Wellcome Trust Senior Investigator Award |
| Amount | £1,500,000 (GBP) |
| Organisation | Wellcome Trust |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 10/2012 |
| End | 09/2017 |
| Title | Exome chip design |
| Description | Contributed to design of Illumina and Affymetrix exome arrays - total sales value of products ~$100,000,000 to date. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2011 |
| Provided To Others? | Yes |
| Impact | Used to support design of commercial arrays |
| Title | Genome wide meta-analysis data sets |
| Description | We have contirbuted in many international consortia to the development of combined data sets (e.g. GIANT - 150,000 samples with genome wide association data) that provide powerful tools for exploration of the genetics of common disease |
| Type Of Material | Biological samples |
| Year Produced | 2007 |
| Provided To Others? | Yes |
| Impact | See publication list e.g. ~10 papers in high impact journals in the past couple of years or so |
| Title | Genome wide meta-analysis infrastructure |
| Description | Through the MRC grant, as well as many of our other funded grants, we have contributed to the development of methodology (and in several cases software - though the software was developed under other funding) to support these studies. |
| Type Of Material | Improvements to research infrastructure |
| Year Produced | 2008 |
| Provided To Others? | Yes |
| Impact | See publications |
| Title | High density arrays |
| Description | We were involved in design and testing of the new Illumina Omni2.5M array |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2010 |
| Provided To Others? | Yes |
| Impact | Commercialised by Illumina. |
| Title | Metabochip |
| Description | Custom iSELECT array for fine mapping and replication of cardiometabolic traits |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | Has been typed on over 200,000 samples so far - publications emerging in coming months |
| Title | DIabetes Knowledge Portal |
| Description | Knowledge portal containing diverse T2D genetic data contributed by multiple groups. In beta-testing. Soft launch early 2015 |
| Type Of Material | Database/Collection of data |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | HAs attracted attention from pharma contribting to development of Accelerating Medicines Partnership between NIH and pharma in the US, now funidng further development of this portal |
| Title | UK exome array |
| Description | Exome array data at both summary and individual data level. Former widely available, latter via EGA |
| Type Of Material | Database/Collection of data |
| Year Produced | 2013 |
| Provided To Others? | Yes |
| Impact | Has contributed to several publications from diverse groups |
| Description | CEED3 |
| Organisation | University of Exeter |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am on the steering committee and lead aspects of one work package. |
| Collaborator Contribution | This supports large-scale data integration and has led to high profile publications and ongoing high profile research. |
| Impact | This supports large-scale data integration relevant to diabetes diagnostics and has led to high profile publications and ongoing high profile research. |
| Start Year | 2008 |
| Description | CHARGE, T2DGENES, PROMIS exome array |
| Organisation | University of California, Los Angeles (UCLA) |
| Department | School of Medicine UCLA |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | WE are collaborating to bring together exome chip data on ~250000 individuals with/without T2D. We bring data from DIAGRAM/T2DGENES |
| Collaborator Contribution | Other groups are bringing data from CHARGE and PROMIS |
| Impact | No outputs as yet |
| Start Year | 2014 |
| Description | CHARGE, T2DGENES, PROMIS exome array |
| Organisation | University of Pennsylvania |
| Department | Perelman School of Medicine |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | WE are collaborating to bring together exome chip data on ~250000 individuals with/without T2D. We bring data from DIAGRAM/T2DGENES |
| Collaborator Contribution | Other groups are bringing data from CHARGE and PROMIS |
| Impact | No outputs as yet |
| Start Year | 2014 |
| Description | DIAGRAM (Diabetes Replication and Meta-analysis) consortium |
| Organisation | Broad Institute |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | My group leads this international effort. |
| Collaborator Contribution | This is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activity |
| Impact | In published work, we have identified ~12 novel T2D susceptibility genes, and in unpublished work (currently submitted or in press) a further 20 or so. This consortium leads international efforts to understand T2D genetics 18372903 19060907 Dupuis et al, NG, in press Other outputs (not directly attributed to MRC funding) 19252133 19526209 18591388 18853133 19056611 19933169. The consortium is now (Oct 2011) preparing publications related to our activities with the metabochip, and on imputation from 1000Genomes into large GWA datasets. |
| Start Year | 2007 |
| Description | DIAGRAM (Diabetes Replication and Meta-analysis) consortium |
| Organisation | Erasmus MC |
| Country | Netherlands |
| Sector | Academic/University |
| PI Contribution | My group leads this international effort. |
| Collaborator Contribution | This is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activity |
| Impact | In published work, we have identified ~12 novel T2D susceptibility genes, and in unpublished work (currently submitted or in press) a further 20 or so. This consortium leads international efforts to understand T2D genetics 18372903 19060907 Dupuis et al, NG, in press Other outputs (not directly attributed to MRC funding) 19252133 19526209 18591388 18853133 19056611 19933169. The consortium is now (Oct 2011) preparing publications related to our activities with the metabochip, and on imputation from 1000Genomes into large GWA datasets. |
| Start Year | 2007 |
| Description | DIAGRAM (Diabetes Replication and Meta-analysis) consortium |
| Organisation | Helmholtz Association of German Research Centres |
| Country | Germany |
| Sector | Academic/University |
| PI Contribution | My group leads this international effort. |
| Collaborator Contribution | This is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activity |
| Impact | In published work, we have identified ~12 novel T2D susceptibility genes, and in unpublished work (currently submitted or in press) a further 20 or so. This consortium leads international efforts to understand T2D genetics 18372903 19060907 Dupuis et al, NG, in press Other outputs (not directly attributed to MRC funding) 19252133 19526209 18591388 18853133 19056611 19933169. The consortium is now (Oct 2011) preparing publications related to our activities with the metabochip, and on imputation from 1000Genomes into large GWA datasets. |
| Start Year | 2007 |
| Description | DIAGRAM (Diabetes Replication and Meta-analysis) consortium |
| Organisation | Imperial College London |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | My group leads this international effort. |
| Collaborator Contribution | This is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activity |
| Impact | In published work, we have identified ~12 novel T2D susceptibility genes, and in unpublished work (currently submitted or in press) a further 20 or so. This consortium leads international efforts to understand T2D genetics 18372903 19060907 Dupuis et al, NG, in press Other outputs (not directly attributed to MRC funding) 19252133 19526209 18591388 18853133 19056611 19933169. The consortium is now (Oct 2011) preparing publications related to our activities with the metabochip, and on imputation from 1000Genomes into large GWA datasets. |
| Start Year | 2007 |
| Description | DIAGRAM (Diabetes Replication and Meta-analysis) consortium |
| Organisation | McGill University |
| Country | Canada |
| Sector | Academic/University |
| PI Contribution | My group leads this international effort. |
| Collaborator Contribution | This is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activity |
| Impact | In published work, we have identified ~12 novel T2D susceptibility genes, and in unpublished work (currently submitted or in press) a further 20 or so. This consortium leads international efforts to understand T2D genetics 18372903 19060907 Dupuis et al, NG, in press Other outputs (not directly attributed to MRC funding) 19252133 19526209 18591388 18853133 19056611 19933169. The consortium is now (Oct 2011) preparing publications related to our activities with the metabochip, and on imputation from 1000Genomes into large GWA datasets. |
| Start Year | 2007 |
| Description | DIAGRAM (Diabetes Replication and Meta-analysis) consortium |
| Organisation | University of Michigan |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | My group leads this international effort. |
| Collaborator Contribution | This is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activity |
| Impact | In published work, we have identified ~12 novel T2D susceptibility genes, and in unpublished work (currently submitted or in press) a further 20 or so. This consortium leads international efforts to understand T2D genetics 18372903 19060907 Dupuis et al, NG, in press Other outputs (not directly attributed to MRC funding) 19252133 19526209 18591388 18853133 19056611 19933169. The consortium is now (Oct 2011) preparing publications related to our activities with the metabochip, and on imputation from 1000Genomes into large GWA datasets. |
| Start Year | 2007 |
| Description | DIAGRAM (Diabetes Replication and Meta-analysis) consortium |
| Organisation | deCODE genetics |
| Country | Iceland |
| Sector | Academic/University |
| PI Contribution | My group leads this international effort. |
| Collaborator Contribution | This is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international collaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activityThis is a large international colaboration that has enabled large-scale association studies in T2D resulting in several publications and ongoing high profile research activity |
| Impact | In published work, we have identified ~12 novel T2D susceptibility genes, and in unpublished work (currently submitted or in press) a further 20 or so. This consortium leads international efforts to understand T2D genetics 18372903 19060907 Dupuis et al, NG, in press Other outputs (not directly attributed to MRC funding) 19252133 19526209 18591388 18853133 19056611 19933169. The consortium is now (Oct 2011) preparing publications related to our activities with the metabochip, and on imputation from 1000Genomes into large GWA datasets. |
| Start Year | 2007 |
| Description | DIRECT |
| Organisation | Eli Lilly & Company Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | This EU IMI grant is worth about €45M. I was part of the writing committee for the final proposal and will lead on one of the major workpackages. The grant officially kicks off in 2012 but the collaboration started in 2010 |
| Collaborator Contribution | Integrates our genetic and genomic appproaches with clinical resources to identify biomarkers able to support stratified medicine for T2D |
| Impact | Success in obtaining approx 45M€ total funding (from the IMI and from pharma) for the DIRECT program of research from 2012 - 2018 |
| Start Year | 2010 |
| Description | DIRECT |
| Organisation | Novo Nordisk |
| Country | Denmark |
| Sector | Private |
| PI Contribution | This EU IMI grant is worth about €45M. I was part of the writing committee for the final proposal and will lead on one of the major workpackages. The grant officially kicks off in 2012 but the collaboration started in 2010 |
| Collaborator Contribution | Integrates our genetic and genomic appproaches with clinical resources to identify biomarkers able to support stratified medicine for T2D |
| Impact | Success in obtaining approx 45M€ total funding (from the IMI and from pharma) for the DIRECT program of research from 2012 - 2018 |
| Start Year | 2010 |
| Description | DIRECT |
| Organisation | Sanofi |
| Department | Aventis |
| Country | France |
| Sector | Private |
| PI Contribution | This EU IMI grant is worth about €45M. I was part of the writing committee for the final proposal and will lead on one of the major workpackages. The grant officially kicks off in 2012 but the collaboration started in 2010 |
| Collaborator Contribution | Integrates our genetic and genomic appproaches with clinical resources to identify biomarkers able to support stratified medicine for T2D |
| Impact | Success in obtaining approx 45M€ total funding (from the IMI and from pharma) for the DIRECT program of research from 2012 - 2018 |
| Start Year | 2010 |
| Description | DIRECT |
| Organisation | Servier Laboratories |
| Country | France |
| Sector | Private |
| PI Contribution | This EU IMI grant is worth about €45M. I was part of the writing committee for the final proposal and will lead on one of the major workpackages. The grant officially kicks off in 2012 but the collaboration started in 2010 |
| Collaborator Contribution | Integrates our genetic and genomic appproaches with clinical resources to identify biomarkers able to support stratified medicine for T2D |
| Impact | Success in obtaining approx 45M€ total funding (from the IMI and from pharma) for the DIRECT program of research from 2012 - 2018 |
| Start Year | 2010 |
| Description | DIRECT |
| Organisation | University of Dundee |
| Department | Biomedical Research Institute |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | This EU IMI grant is worth about €45M. I was part of the writing committee for the final proposal and will lead on one of the major workpackages. The grant officially kicks off in 2012 but the collaboration started in 2010 |
| Collaborator Contribution | Integrates our genetic and genomic appproaches with clinical resources to identify biomarkers able to support stratified medicine for T2D |
| Impact | Success in obtaining approx 45M€ total funding (from the IMI and from pharma) for the DIRECT program of research from 2012 - 2018 |
| Start Year | 2010 |
| Description | DOLORISK |
| Organisation | University of Dundee |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | WE are responsible for the genetics WP of this H2020 consortium |
| Collaborator Contribution | Dundee (and other partners not listed) have provided samples for us to GWAS |
| Impact | Still in progress |
| Start Year | 2016 |
| Description | EGG (Early Growth Genetics) consortium |
| Organisation | University of Bristol |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We lead this effort which has so far netted the first common variants influencing birth weight and promises to result in insights into other early growth phenotypes |
| Collaborator Contribution | This is a large international colaboration that has enabled large-scale association studies in early growth genetics resulting in several publications and ongoing high profile research activity |
| Impact | This is a large international colaboration that has enabled large-scale association studies in early growth genetics resulting in several publications and ongoing high profile research activity. We published on BW in Nature Genetics in 2010, and there are ~10 further high profile publications under review or in preparation from the wider consortium relating the genetic basis of many early growth phenotypes. |
| Start Year | 2008 |
| Description | ENGAGE (European Network for Genetic and Genomic Epidemiology) |
| Organisation | The Wellcome Trust Sanger Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | I co-lead this effort with Leena Peltonen of the SAnger,and following her death am the coordinator. It is funded by the EU (FP7) |
| Collaborator Contribution | This supports large-scale data integration and has led to high profile publications and ongoing high profile research. |
| Impact | This supports large-scale data integration and has led to high profile publications and ongoing high profile research. Work arising has not had direct MRC funding but includes 19060911 19503597 19060910 |
| Start Year | 2008 |
| Description | EpiMIGRANT |
| Organisation | Imperial College London |
| Department | School of Public Health |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am part of the leadership team for the EU award and wil lead one of the WPs |
| Collaborator Contribution | Will enable large-scale epigenetic analysis of South Asians with and without T2D.Epigenomics of T2D in South AsiansEpugenomics of T2D in south Asians |
| Impact | The project starts in 2012. |
| Start Year | 2010 |
| Description | EpiMIGRANT |
| Organisation | International Diabetes Institute (IDI) |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | I am part of the leadership team for the EU award and wil lead one of the WPs |
| Collaborator Contribution | Will enable large-scale epigenetic analysis of South Asians with and without T2D.Epigenomics of T2D in South AsiansEpugenomics of T2D in south Asians |
| Impact | The project starts in 2012. |
| Start Year | 2010 |
| Description | EpiMIGRANT |
| Organisation | University of Cambridge |
| Department | Strangeways Research Laboratory |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | I am part of the leadership team for the EU award and wil lead one of the WPs |
| Collaborator Contribution | Will enable large-scale epigenetic analysis of South Asians with and without T2D.Epigenomics of T2D in South AsiansEpugenomics of T2D in south Asians |
| Impact | The project starts in 2012. |
| Start Year | 2010 |
| Description | GIANT (Genetic Investigation of Anthropometric Traits) Consortium |
| Organisation | Harvard University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We co-lead this effort, contributing data and analysis and expertise to the study of the genetics of height, BMI and central obesity phenotypes. |
| Collaborator Contribution | This is a large international colaboration that has enabled large-scale association studies in anthropometric traits resulting in several publications and ongoing high profile research activity |
| Impact | This is a large international colaboration that has enabled large-scale association studies in anthropometric traits resulting in several publications and ongoing high profile research activity 18454148 19079261 OTher outputs (not directly funded by MRC) but arising from the partnership 17767157 18346983 18391952 18842783 19005641 19557161 |
| Start Year | 2007 |
| Description | GTEX |
| Organisation | Center for Human Genetic Research; Broad Institute |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I lead one component of the analytical research related ot the GTEX project, as part of a recurrent R01 award held by PI Dermitzakis |
| Collaborator Contribution | We have contributed analyses relating expresison data to GWAS signals |
| Impact | Several papers emerging including 24037378 |
| Start Year | 2009 |
| Description | GTEX |
| Organisation | Stanford University |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | I lead one component of the analytical research related ot the GTEX project, as part of a recurrent R01 award held by PI Dermitzakis |
| Collaborator Contribution | We have contributed analyses relating expresison data to GWAS signals |
| Impact | Several papers emerging including 24037378 |
| Start Year | 2009 |
| Description | GTEX |
| Organisation | University of Geneva |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | I lead one component of the analytical research related ot the GTEX project, as part of a recurrent R01 award held by PI Dermitzakis |
| Collaborator Contribution | We have contributed analyses relating expresison data to GWAS signals |
| Impact | Several papers emerging including 24037378 |
| Start Year | 2009 |
| Description | Genetics of Type 2 diabetes (GoT2D) |
| Organisation | Broad Institute |
| Department | Medical and Population Genetics Program |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Oxford is jointly responsible for this high profile project funded to a total of $20M by the NIH, another $10M by NHGRI and £2.5M by the Wellcome Trust. We are undertaking whole genome sequencing of 650 individuals |
| Collaborator Contribution | We are jointly responsible for the largest study in type 2 diabetes genetics currently ongoing - including whole genome sequencing of 2650 individuals. see under Broad |
| Impact | Multidiscipinary - genetics, genomics, statistics, informatics. Data generation at present. High profile publications expected in due course. We have (Oct 2011) almost completed data generation (~2850 samples with whole genome, whole exome and dense genotype data) and proceeding to analysis |
| Start Year | 2009 |
| Description | Genetics of Type 2 diabetes (GoT2D) |
| Organisation | University of Michigan |
| Department | University of Michigan Medical School |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Oxford is jointly responsible for this high profile project funded to a total of $20M by the NIH, another $10M by NHGRI and £2.5M by the Wellcome Trust. We are undertaking whole genome sequencing of 650 individuals |
| Collaborator Contribution | We are jointly responsible for the largest study in type 2 diabetes genetics currently ongoing - including whole genome sequencing of 2650 individuals. see under Broad |
| Impact | Multidiscipinary - genetics, genomics, statistics, informatics. Data generation at present. High profile publications expected in due course. We have (Oct 2011) almost completed data generation (~2850 samples with whole genome, whole exome and dense genotype data) and proceeding to analysis |
| Start Year | 2009 |
| Description | H3Africa |
| Organisation | The Wellcome Trust Sanger Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | I am part of the H3A funded project on diabetes in Africa. |
| Collaborator Contribution | We have designed and are now implementing a large collection of T2D cases and controls in Africa |
| Impact | None as yet |
| Start Year | 2010 |
| Description | H3Africa |
| Organisation | University of Cape Town |
| Country | South Africa |
| Sector | Academic/University |
| PI Contribution | I am part of the H3A funded project on diabetes in Africa. |
| Collaborator Contribution | We have designed and are now implementing a large collection of T2D cases and controls in Africa |
| Impact | None as yet |
| Start Year | 2010 |
| Description | H3Africa |
| Organisation | University of KwaZulu-Natal |
| Country | South Africa |
| Sector | Academic/University |
| PI Contribution | I am part of the H3A funded project on diabetes in Africa. |
| Collaborator Contribution | We have designed and are now implementing a large collection of T2D cases and controls in Africa |
| Impact | None as yet |
| Start Year | 2010 |
| Description | MAGIC (Meta-analysis of Glycaemic and Insulin related traits) Consortium |
| Organisation | The Wellcome Trust Sanger Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | We co-lead this collaboration of over 70 groups worldwide (it is impractical for me to enter the details in this form) working on the genetic basis of glycemic traits. |
| Collaborator Contribution | This is a large international colaboration that has enabled large-scale association studies in continuous glycemic traits resulting in several publications and ongoing high profile research activity |
| Impact | This group has identified ~20 genome wide significant signals influencing continuous glycemic traits, a subset of which also influence T2D risk. This has resulted in a number of high profile publications (qv). 19060907 Dupuis et al, NG, 2010. Further publications have arisen over the past few years, and a new batch of publications is currently (Oct 2011) being prepared related to metabochip data. |
| Start Year | 2008 |
| Description | METABOCHIP consortium |
| Organisation | University of Michigan |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | We co-lead this effort. |
| Collaborator Contribution | This is a large international colaboration that has designed a chip to enable largescale replication and fine mapping of several cardiovascular and metabolic traits. The typing and analysis of these data are ongoing. |
| Impact | This is a large international colaboration that has designed a chip to enable largescale replication and fine mapping of several cardiovascular and metabolic traits. The typing and analysis of these data are ongoing. |
| Start Year | 2008 |
| Description | Mendelian Randomisation to help identify potential adverse effects of drug treatments |
| Organisation | GlaxoSmithKline (GSK) |
| Country | Global |
| Sector | Private |
| PI Contribution | We are working with GSK to perform genetic tests to understand potential adverse effects of cardio vascular drug treatments. These include those affecting the HIF pathway and anaemia in Chronic kidney disease such as EPO stimulating agents. |
| Collaborator Contribution | GSK are providing the expertise in cardio vascular endpoints and contributing financially to staff in Exeter. This collaboration stimulated an MRC CASE studentship award which will begin in September 2017. |
| Impact | Too early |
| Start Year | 2016 |
| Description | Metagenetic risk profiles |
| Organisation | University of Melbourne |
| Country | Australia |
| Sector | Academic/University |
| PI Contribution | Data sharing |
| Collaborator Contribution | Methods sharing |
| Impact | None as yet |
| Start Year | 2018 |
| Description | PAGE consortium |
| Organisation | University of California, Los Angeles (UCLA) |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Collaboration to design and genotype a transethnic genotyping array |
| Collaborator Contribution | With T2DGENES colleagues we designed the array |
| Impact | Design of an array |
| Start Year | 2013 |
| Description | RHAPSODY |
| Organisation | University of Lausanne |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | My group coleads WP5 in this IMI consortium |
| Collaborator Contribution | There are around 20 academic groups and 5 pharma companies involved in this consortium |
| Impact | Still in early stages |
| Start Year | 2016 |
| Description | STEMBANCC |
| Organisation | Eli Lilly & Company Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | This is a new IMI collaboration (total funding 53M€ from IMI and in kind) to Oxford and 25 other academic institutions. |
| Collaborator Contribution | We will provide clinical material (from patients), characterise stem cell derived tissues derived and manage the diabetes work package |
| Impact | Nil to date |
| Start Year | 2012 |
| Description | STEMBANCC |
| Organisation | F. Hoffmann-La Roche AG |
| Country | Global |
| Sector | Private |
| PI Contribution | This is a new IMI collaboration (total funding 53M€ from IMI and in kind) to Oxford and 25 other academic institutions. |
| Collaborator Contribution | We will provide clinical material (from patients), characterise stem cell derived tissues derived and manage the diabetes work package |
| Impact | Nil to date |
| Start Year | 2012 |
| Description | STEMBANCC |
| Organisation | Novo Nordisk |
| Country | Denmark |
| Sector | Private |
| PI Contribution | This is a new IMI collaboration (total funding 53M€ from IMI and in kind) to Oxford and 25 other academic institutions. |
| Collaborator Contribution | We will provide clinical material (from patients), characterise stem cell derived tissues derived and manage the diabetes work package |
| Impact | Nil to date |
| Start Year | 2012 |
| Description | STEMBANCC |
| Organisation | Sanofi |
| Department | Aventis |
| Country | France |
| Sector | Private |
| PI Contribution | This is a new IMI collaboration (total funding 53M€ from IMI and in kind) to Oxford and 25 other academic institutions. |
| Collaborator Contribution | We will provide clinical material (from patients), characterise stem cell derived tissues derived and manage the diabetes work package |
| Impact | Nil to date |
| Start Year | 2012 |
| Description | SUMMIT |
| Organisation | AstraZeneca |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | I am one of the leaders of the consortium with responsiblity specifically for the GWA studies of diabetes complciations at the core of the proposal. It has been funded to a total of €28M by the EU and EFPIA partners under the IMI initiative |
| Collaborator Contribution | This project is funded by EU-IMI. WE lead WP1, have analysed most of teh GWAS data and performed and analysed exome sequencing data. Publications anticipated 2013. |
| Impact | Tangible ouput is 30M euros of funding from EU and pharma Publications 2013 |
| Start Year | 2009 |
| Description | SUMMIT |
| Organisation | Boehringer Ingelheim |
| Country | Germany |
| Sector | Private |
| PI Contribution | I am one of the leaders of the consortium with responsiblity specifically for the GWA studies of diabetes complciations at the core of the proposal. It has been funded to a total of €28M by the EU and EFPIA partners under the IMI initiative |
| Collaborator Contribution | This project is funded by EU-IMI. WE lead WP1, have analysed most of teh GWAS data and performed and analysed exome sequencing data. Publications anticipated 2013. |
| Impact | Tangible ouput is 30M euros of funding from EU and pharma Publications 2013 |
| Start Year | 2009 |
| Description | SUMMIT |
| Organisation | Eli Lilly & Company Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | I am one of the leaders of the consortium with responsiblity specifically for the GWA studies of diabetes complciations at the core of the proposal. It has been funded to a total of €28M by the EU and EFPIA partners under the IMI initiative |
| Collaborator Contribution | This project is funded by EU-IMI. WE lead WP1, have analysed most of teh GWAS data and performed and analysed exome sequencing data. Publications anticipated 2013. |
| Impact | Tangible ouput is 30M euros of funding from EU and pharma Publications 2013 |
| Start Year | 2009 |
| Description | SUMMIT |
| Organisation | F. Hoffmann-La Roche AG |
| Country | Global |
| Sector | Private |
| PI Contribution | I am one of the leaders of the consortium with responsiblity specifically for the GWA studies of diabetes complciations at the core of the proposal. It has been funded to a total of €28M by the EU and EFPIA partners under the IMI initiative |
| Collaborator Contribution | This project is funded by EU-IMI. WE lead WP1, have analysed most of teh GWAS data and performed and analysed exome sequencing data. Publications anticipated 2013. |
| Impact | Tangible ouput is 30M euros of funding from EU and pharma Publications 2013 |
| Start Year | 2009 |
| Description | SUMMIT |
| Organisation | Lund University |
| Country | Sweden |
| Sector | Academic/University |
| PI Contribution | I am one of the leaders of the consortium with responsiblity specifically for the GWA studies of diabetes complciations at the core of the proposal. It has been funded to a total of €28M by the EU and EFPIA partners under the IMI initiative |
| Collaborator Contribution | This project is funded by EU-IMI. WE lead WP1, have analysed most of teh GWAS data and performed and analysed exome sequencing data. Publications anticipated 2013. |
| Impact | Tangible ouput is 30M euros of funding from EU and pharma Publications 2013 |
| Start Year | 2009 |
| Description | SUMMIT |
| Organisation | Pfizer Ltd |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | I am one of the leaders of the consortium with responsiblity specifically for the GWA studies of diabetes complciations at the core of the proposal. It has been funded to a total of €28M by the EU and EFPIA partners under the IMI initiative |
| Collaborator Contribution | This project is funded by EU-IMI. WE lead WP1, have analysed most of teh GWAS data and performed and analysed exome sequencing data. Publications anticipated 2013. |
| Impact | Tangible ouput is 30M euros of funding from EU and pharma Publications 2013 |
| Start Year | 2009 |
| Description | T2D-GENES |
| Organisation | Broad Institute |
| Department | Medical and Population Genetics Program |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Collaborator Contribution | Overall program is funded to a total of $24M so far and designed to encourage transethnic studies in t2D genetics. Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Impact | Data generation currently, based around next-generation sequencing. We expect high profile publications in 2013. |
| Start Year | 2009 |
| Description | T2D-GENES |
| Organisation | National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) |
| Country | United States |
| Sector | Charity/Non Profit |
| PI Contribution | Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Collaborator Contribution | Overall program is funded to a total of $24M so far and designed to encourage transethnic studies in t2D genetics. Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Impact | Data generation currently, based around next-generation sequencing. We expect high profile publications in 2013. |
| Start Year | 2009 |
| Description | T2D-GENES |
| Organisation | University of Chicago |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Collaborator Contribution | Overall program is funded to a total of $24M so far and designed to encourage transethnic studies in t2D genetics. Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Impact | Data generation currently, based around next-generation sequencing. We expect high profile publications in 2013. |
| Start Year | 2009 |
| Description | T2D-GENES |
| Organisation | University of Michigan |
| Department | University of Michigan Medical School |
| Country | United States |
| Sector | Academic/University |
| PI Contribution | Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Collaborator Contribution | Overall program is funded to a total of $24M so far and designed to encourage transethnic studies in t2D genetics. Oxford is on the steering committee of the project, and also heads one of the five funded consortia within the effort. We play a major role in planning, sample provision, analysis and informatics. |
| Impact | Data generation currently, based around next-generation sequencing. We expect high profile publications in 2013. |
| Start Year | 2009 |
| Description | The MUTHER (Multiple Tissues for Human Expression Resource) Consortium |
| Organisation | King's College Hospital |
| Country | United Kingdom |
| Sector | Hospitals |
| PI Contribution | We have contributed to sample preparation, database design and to data analysis |
| Collaborator Contribution | it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. |
| Impact | We have assembled one of the largest tissue expression banks available and are instituting detailed analysis. Two papers have already been published in high profile journals (Nica, PLoS GENETICS 2010; Small Nature genetics 2011) and further publications are in preparation as of Oct 2011. |
| Start Year | 2007 |
| Description | The MUTHER (Multiple Tissues for Human Expression Resource) Consortium |
| Organisation | The Wellcome Trust Sanger Institute |
| Country | United Kingdom |
| Sector | Charity/Non Profit |
| PI Contribution | We have contributed to sample preparation, database design and to data analysis |
| Collaborator Contribution | it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. |
| Impact | We have assembled one of the largest tissue expression banks available and are instituting detailed analysis. Two papers have already been published in high profile journals (Nica, PLoS GENETICS 2010; Small Nature genetics 2011) and further publications are in preparation as of Oct 2011. |
| Start Year | 2007 |
| Description | The MUTHER (Multiple Tissues for Human Expression Resource) Consortium |
| Organisation | University of Geneva |
| Country | Switzerland |
| Sector | Academic/University |
| PI Contribution | We have contributed to sample preparation, database design and to data analysis |
| Collaborator Contribution | it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. it has supported methods development, and provided samples and a collaborative network for analysis of expression and methylation data relevant to multiple human traits. |
| Impact | We have assembled one of the largest tissue expression banks available and are instituting detailed analysis. Two papers have already been published in high profile journals (Nica, PLoS GENETICS 2010; Small Nature genetics 2011) and further publications are in preparation as of Oct 2011. |
| Start Year | 2007 |
| Description | Wellcome Trust Case Control Consortium (extension) |
| Organisation | Institute of Cancer Research UK |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | We lead the T2D component of this work as well as contributing to study design and analysis. |
| Collaborator Contribution | We collaborate to understand the impact of CNVs on common disease predisposition and to fine map causal variants for these diseases. |
| Impact | This has led to pioneering work in the field - the first papers are currently under review at Nature and other journals. |
| Start Year | 2007 |
| Description | genetics and peptides |
| Organisation | Novo Nordisk |
| Country | Denmark |
| Sector | Private |
| PI Contribution | We provide access to T2D GWAS and sequencing data; |
| Collaborator Contribution | NN provides lists of peptides |
| Impact | None as yet |
| Start Year | 2017 |
| Title | ~150 common variant signals underlying common diseases |
| Description | We have contributed (using MRC funds wholy or in part) to identification of many genes influencing T2D, BMI and other related phenotypes (see publications). We regard these discoveries as pre competitive (in line with NIH and other recommendations) and have DELIBERATELY chosen not to seek protection. We regard protection of such discoveries as counter productive from the point of view of biological and translational advance. |
| IP Reference | |
| Protection | Protection not required |
| Year Protection Granted | 2007 |
| Licensed | No |
| Impact | We believe that by sharing these findings as early as possible through publication and without any protection that we support rapid scientific progression and future translational usage. |
| Description | American Society of Nephrology, meeting, New Orleans |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Workshop and talk at ASN 2017 |
| Year(s) Of Engagement Activity | 2017 |
| Description | Cafe Scientifique - Exeter |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | A 40-45 minute presentation to a lay audience followed by 45 minutes of questions and answers. This was mainly around the "fat gene" story, but all aspects of human genetics were discussed. There was lots of interest from the audience who asked plenty of searching questions! A member of the audience interviewed me for a piece in Devon Country Life magazine, which increased the impact of the research. |
| Year(s) Of Engagement Activity | 2009 |
| Description | Conference on personalised nutrition, Shanghai China |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | International conference on personalised nutrition organised by Chinese colleagues |
| Year(s) Of Engagement Activity | 2017 |
| Description | DNA testing: "Science or Swindle?" |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | This was a public seminar hosted by the DANA centre at the Science Museum, London. I was one of four scientists giving a brief presentation followed by four question and answer sessions. The topic was direct to consumer DNA tests that companies such as DecodeMe and 23andMe are offering. Lots of questions and comments from a lay audience. For myself, an improved understanding of the public's perceptions of human genetics. For the public, hopefully an improved understanding of human genetics. |
| Year(s) Of Engagement Activity | 2009 |
| Description | Diabetes UK Professional Conference Insider Event March 9, 2019 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Bringing scientific highlights from the Professional Conference of Diabetes UK to members of the organisation. |
| Year(s) Of Engagement Activity | 2019 |
| Description | Diabetes UK patient and volunteer conference |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Regional |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | A presentation followed by question and answer session to >300 Diabetic patients and fundraisers at their annual conference in Manchester, October 2009. I was the only presenter invited to talk about type 2 diabetes related research, along with one presenter invited to talk about type 1 diabetes. Considerable interest in the question and answer session. Hopefully an improved understanding by the patients of what we learn from their DNA samples. |
| Year(s) Of Engagement Activity | 2009 |
| Description | Diabetes UK patients and fundraisers |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Public/other audiences |
| Results and Impact | Presentation adn QandA session to diabetes patients and fundraisers at the DIabetes UK annual conference. Interest from audience and further invites to other groups |
| Year(s) Of Engagement Activity | 2009 |
| Description | East Meets West Conference Hong Kong |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Lecture, debates, discussions about diabetes genetics in East Asia and beyond |
| Year(s) Of Engagement Activity | 2016 |
| Description | Genomics for Clinicians meeting |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | I gave a presentation at this 4 day workshop on the value of diabetes genetics in genomic medicine |
| Year(s) Of Engagement Activity | 2017 |
| Description | International Diabetes federation, Abu DHabi |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | PResentation at IDF meeting |
| Year(s) Of Engagement Activity | 2017 |
| Description | Interview for Medscape |
| Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Interview on Medscape related to personalised medicine for diabetes |
| Year(s) Of Engagement Activity | 2019 |
| Description | NovoNordisk Workshop on Early Growth genetics |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Part of a discussion about the role of genes and environment on the relationship between early growth and later metabolic disease |
| Year(s) Of Engagement Activity | 2017 |
| Description | Personalised genomics |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Public/other audiences |
| Results and Impact | Public debate; conference presentations Improved understanding of the issues by the audience |
| Year(s) Of Engagement Activity | 2009,2012,2013,2015,2016 |
| Description | Personalised medicine Symposium, Bastad Sweden |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Postgraduate students |
| Results and Impact | Part of a symposium on Personalised Medicine held in Sweden |
| Year(s) Of Engagement Activity | 2016 |
| Description | Pint of Science |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Public/other audiences |
| Results and Impact | A talk on obesity genetics at a local pub. "Pint of Science" was sponsored by the Wellcome Trust and eLIFE |
| Year(s) Of Engagement Activity | 2016 |
| Description | Progress Education Trust |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Health professionals |
| Results and Impact | Workshop/Seminar on hype in genetics discussions, followup contacts |
| Year(s) Of Engagement Activity | 2009 |
| Description | Scientific presentations and seminars |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Type Of Presentation | Keynote/Invited Speaker |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Data from these two grants has been presented at a large number of international meetings including American Diabetes Association, American Soc Human Genetics, Genomics of Common Diseases and other meetings (approx 20 a year) Large audiences |
| Year(s) Of Engagement Activity | 2012,2013,2015,2016 |
| Description | Short article in study participants' newsletter. |
| Form Of Engagement Activity | A magazine, newsletter or online publication |
| Part Of Official Scheme? | Yes |
| Geographic Reach | Local |
| Primary Audience | Patients, carers and/or patient groups |
| Results and Impact | Short articles describing our research on diabetes and birth weight genes aimed at patients and research volunteers who had contributed DNA and phenotype information from themselves and in some cases, their offspring. A greater understanding of genetic research by the study participants - in Exeter we have successfully recruited a large number of individuals to genetic studies. Virtually no-one declines to take part in a study on the grounds that they are suspicious of genetic research. Although hard to prove we hope that our "user-friendly" dissemination is part of the reason for this success. |
| Year(s) Of Engagement Activity | 2007,2008,2009,2010,2011 |
| Description | Wellcome Trust - Artists |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Public/other audiences |
| Results and Impact | Describing genetic research to artists and those in visual media interesting in applying to Wellcome Trust Arts-related funding Informed projects submitted to WT for funding |
| Year(s) Of Engagement Activity | 2008 |
| Description | Wellcome Trust - Journalists |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Media (as a channel to the public) |
| Results and Impact | Lectures to and meetings with science journalists. In addition, frequent contacts with national and international journalists to comment on stories, provide quotes etc Newspapers, online media, radio, quotes, articles |
| Year(s) Of Engagement Activity | 2007,2009,2012,2013 |
| Description | chinese diabetes society, Chongqing |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | Presentation to several thousand people at Chinese DIabetes Association |
| Year(s) Of Engagement Activity | 2017 |