Accessible resource for integrated epigenomics studies (ARIES)

Lead Research Organisation: Newcastle University
Department Name: Institute of Human Genetics

Abstract

Epigenetic studies are becoming a central focus of biological research internationally. Epigenetic profiles can serve as exposure markers and as prognostic or predictive biomarkers, with leukocyte methylation currently being the most commonly measured form of epigenetic modification, in the most readily obtainable tissue and one that has undergone epigenetic analysis in many investigations. In regard to this mode of analysis the Avon Longitudinal Study of Parents and their Children (ALSPAC) provides a unique potential resource, in having two-generational data and cord blood and later peripheral blood samples available, allowing for intrauterine influences, intergenerational transmission, change in methylation from birth through to pre-pubertal and post-pubertal age, and investigation of how methylation patterns predict and change with development. Such methylation data would be linked to the extensive exposure, genotype and phenotype data available in ALSPAC. The human data will be coupled with rodent data documenting the relationship between leukocyte and other tissue methylation and gene expression and rodent model tissue banks related to over-nutrition, obesity and ageing. Additional rodent tissues will be banked for future analysis upon request. Data generated will be uploaded for browsing on a custom web-based interface developed specifically for this initiative which will permit the integration of data from multiple sources from both human and rodent sources. The user will have access to data exploration utilities, a graphical genome browser and interactive graphical views of data relationships. The integration of data on epigenetic profiles in this intensively characterised human cohort with rodent epigenetic and transcriptomic data to generate an accessible resource to enhance research in the field of epigenetics for the benefit of the wider scientific community represents a considerable bioinformatic undertaking. We will draw on the expertise of leading scientists in the field of epigenetics and population-based human cohort studies to generate relevant data and combine this with up to date and highly skilled bioinformatics input (developed with substantive previous investment from the BBSRC) to meet our stated objectives. In combination, the proposed generation of biological data together with state of the art bioinformatic tools for data integration and access, would provide an unequivocally world-leading resource for epigenetic studies.

Technical Summary

Serial samples taken at multiple time points across the lifecourse from 1,000 mother-child pairs from ALSPAC will be used to generate genome-wide DNA methylation. The Illumina 450K human methylation array will be used to analyse samples from birth, age 7 and age 15-17 in 1,000 children and samples taken during pregnancy and 17 years later from their mothers. These data will be complemented by methylome sequencing of both the 5-methylcytosine and 5-hyroxymethylcytosine fractions of the genome which will be isolated by immuno-precipitation and sequenced using a next-generation platform. Tandem genome wide methylation and gene expression analysis will be undertaken in mouse tissues (leukocytes, adipose, muscle, liver) using a custom NimbleGen methylation array and Affymetrix gene ST arrays respectively. Further mouse tissues will be harvested and banked for future investigation upon request. The complex primary data generated will be processed and fully integrated using the Ondex system that has been developed under the SABR initiative. In addition to the facility to view these data in an open access browser, users will have the opportunity to access extensive exposure and phenotype information from the ALSPAC cohort using the existing infrastructure. The project will run for 2 years and be managed by a team of academics who have a proven track record in large scale collaborative research and the provision of data and information to the wider scientific community. An international Scientific Advisory Board of leading scientists in epigenetics and bioinformatics will contribute to the oversight of ARIES.

Planned Impact

The ARIES project draws together complementary skills in laboratory, population and bioinformatic aspects of epigenetics to create a unique resource that will be of considerable value to a broad bioscience community spanning both academia and industry, both in the UK and internationally. The population of researchers engaged in the field of epigenetics is growing exponentially and the need for large scale genome-wide locus specific epigenomic data in combination with phenotypic and exposure data has been identified as a research priority by several recent high impact publications. Such information would provide understanding of how the epigenome differs between individuals, how it changes through the life course during the natural ageing process, identify factors that mediate these changes and provide insight into their physiological consequences. The ARIES project will address this knowledge and resource deficit by capitalising on recent advances in genome wide epigenetic methodologies and the availability of samples from a unique parent and child cohort (ALSPAC) which has been extensively phenotypically and genetically characterised over the past 20 years. The inclusion of data from mice to address tissue-specificity of the epigenotype, another major focus of current debate in the field, provides an extra and important dimension. The project will utilise advanced bioinformatic tools to establish a facility to amass, integrate and disseminate multi-dimensional biological information. The incorporation of computational tools and web-based technology is increasingly a feature of scientific research and this project will exemplify the societal impact that such advances can have. As reflected by the letters of support from both academia and industry in the UK, Europe and further afield, the ARIES resource will be utilised widely and accelerate scientific advances in this rapidly emerging field. The proposed timescale of 2 years places ARIES in a highly competitive position, with tangible output well in advance of much larger, more technically demanding global initiatives currently being discussed. Epigenetics has captured the headlines in both the popular and scientific press in recent years partly due to the promise it holds in providing a route through which gene expression can be modulated by pharmacological, dietary, lifestyle or perhaps behavioural interventions. This is particularly important in modern society where in countries such as the UK, the population is ageing and governments are faced with ensuring that the 'health span' of the population increases in parallel with the 'lifespan'. Furthermore, epigenetic mechanisms are clearly important in optimal development, and possible cognitive (and other) deficits of considerable importance in economic and human capital terms may arise through such processes. Any interventions that optimise development and ageing could therefore have a major societal impact. Research in this field is actively being pursued in many domains from basic science laboratories to the pharmaceutical industry. Industrial colleagues have therefore justifiably highlighted the potential that ARIES represents in enhancing the efforts in preventive medicine, the discovery of novel therapeutic targets and the possible application of epigenetic factors as biomarkers of efficacy of interventions and treatments. Modification of the epigenotype is a considerably more tractable target for intervention and prevention strategies than modification of the genotype and therefore has the potential to make a greater impact on public health policies and the wellbeing of the population. Advances in any of these areas would bring considerable economic gain and maintain the UK at the forefront of advances in this area.

Publications

10 25 50

 
Description This award developed an internationally leading resource of epigenetic data that has been used widely and continues to be a valuable resource.
Exploitation Route Through continued use of epigenetic data linked to a world leading longitudinal cohort study.
Through the development and application of statistical methods and bioinformatic tools to analyse these epigenetic data
Through leadership and participation in large scale international consortia to utilise such epigenetic data.
Data are increasing used in applied research to address specific questions about the role of epigenetic processes in development and disease.
More recently ARIES is being used by social scientists (in cross-council funded projects) to understand how social factors become embodied in phenotype.
Sectors Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology

URL http://www.ariesepigenomics.org.uk/ariesexplorer
 
Description The output from the ARIES project has been widely used. It forms a major component of my MRC Epigenetic Epidemiology Programme. Dozens of collaborators nationally and internationally use the data for their research. More than 10% of data requests from the ALSPAC study are for epigenetic data generated by ARIES.
First Year Of Impact 2014
Sector Digital/Communication/Information Technologies (including Software),Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description A statistical framework for epigenetic change
Amount £298,482 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 10/2015 
End 09/2018
 
Description ARIES Brazil - BBSRC Parnering Award
Amount £50,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 01/2013 
End 12/2015
 
Description Creating a West African BioResource for Nutritional Genetics and Epigenetics (C Relton)
Amount £186,171 (GBP)
Funding ID MC_PC_MR/R020183/1 
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 01/2018 
End 12/2018
 
Description De Pass Vice Chancellor's Fellowship - Rebecca Richmond
Amount £260,000 (GBP)
Organisation University of Bristol 
Sector Academic/University
Country United Kingdom
Start 10/2018 
End 10/2022
 
Description Development of new statistical frameworks for causal analyses utilizing of multiple omics datasets - Sponsor
Amount £300,000 (GBP)
Organisation Oak Foundation 
Sector Charity/Non Profit
Country Global
Start 11/2012 
End 10/2016
 
Description Does prematurity impair child health via epigenetics? Co-I
Amount £132,000 (GBP)
Organisation Women's and Children's Hospital Foundation 
Sector Charity/Non Profit
Country Australia
Start 01/2013 
End 12/2015
 
Description ERA-HDHL - Early life programming of childhood health: a nutritional and epigenetic investigation of adiposity and bone, cardiometabolic, neurodevelopmental and respiratory health.
Amount £124,600 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 04/2017 
End 12/2019
 
Description ESRC - Co-Investigator (PI Davey Smith G)
Amount £250,000 (GBP)
Organisation Economic and Social Research Council 
Sector Public
Country United Kingdom
Start 09/2013 
End 03/2015
 
Description Epigenetic biomarkers in neurodegenerative disease
Amount £78,388 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 09/2013 
End 08/2015
 
Description Genomic and environmental risk for cardiometabolic disease in Africans. Consultant
Amount $2,500,000 (USD)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 09/2012 
End 08/2017
 
Description HDR UK RCUK Innovation/Rutherford Fellowships - Two fellowships (C Relton)
Amount £614,457 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 02/2018 
End 01/2021
 
Description MRC Centenary Award - Co-Investigator (PI Fraser A)
Amount £100,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2013 
End 08/2014
 
Description Mechanistic insights from birth cohorts
Amount $2,500,000 (USD)
Funding ID NIH PAR-13-009 
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 10/2014 
End 09/2019
 
Description Medical Research Council
Amount £1,100,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 06/2013 
End 03/2018
 
Description NIH - Childhood adversity, DNA methylation and risk for depression: A longitudinal study of sensitive periods in development.
Amount $1,623,764 (USD)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 10/2017 
End 10/2019
 
Description Pfizer
Amount £175,000 (GBP)
Organisation Pfizer Ltd 
Sector Private
Country United Kingdom
Start 12/2013 
End 06/2015
 
Description Roy Castle Lung Cancer Foundation
Amount £74,990 (GBP)
Organisation Roy Castle Lung Cancer Foundation 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2013 
End 03/2015
 
Description The role of DNA methylation in type 2 diabetes and insulin sensitivity - Sponsor
Amount £300,000 (GBP)
Organisation Oak Foundation 
Sector Charity/Non Profit
Country Global
Start 09/2012 
End 08/2016
 
Title Meffil - J.Min 
Description Josine Min and other researchers have developed a new tool for performing quality control and preprocessing large sets of DNA methylation profiles used in epidemiological studies. Previous tools were unable to process such large datasets without requiring high-end computational resources. Our tool may also be used to improve statistical power in meta-analyses. 
Type Of Material Improvements to research infrastructure 
Year Produced 2018 
Provided To Others? Yes  
Impact This package has been used to analyse 36 datasets from the GoDMC consortium. It has been cited by 7 publications. 
URL https://github.com/perishky/meffil#meffil
 
Title ARIES Explorer 
Description ARIES Explorer - data available via ALSPAC data access process 
Type Of Material Data handling & control 
Year Produced 2013 
Provided To Others? Yes  
Impact The ARIES-Explorer web interface was launched on the resource website (http://www.ariesepigenomics.org.uk) in November 2013. AWStats analysis of webserver log files show that in the first month following data release (Nov 2013) the website received 872 visits from 419 unique visitors (250MB of data transferred). The site is indexed by Google, Bing and Baidu and currently receives around 50 hits per day. 
URL http://www.ariesepigenomics.org.uk
 
Title EWAS Catalog 
Description A database of epigenome-wide association studies with seacrh tool 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact None as yet 
URL http://www.ewascatalog.org
 
Title Genetics of DNA methylation Consortium (GoDMC) - Josine Min 
Description As part of the GoDMC (Genetics of DNA methylation Consortium) we have generated a database which contains all discovered mQTL associations. It also has a dalliance genome browser to explore regional features of the association. 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? No  
Impact We have developed a github pipeline for the GoDMC consortium. So far, 36 different groups have processed and analysed their data and uploaded the results to our sftp server. 
 
Title GoDMC github repository 
Description This is a github repository developed for the GoDMC. 30+ GoDMC cohorts will download the pipeline and will follow instructions to run the pipeline. Briefly, the analyses are splitted into 3 broad stages: 1. Formatting data into the correct shape for the pipeline 2. Running the pipeline to perform data checks, transformations, data processing and stage 1 analysis for meQTLs, EWAS and GWAS. This is currently partitioned into 15 modules, and after running each module the summary level results are checked and uploaded to a SFTP server in Bristol. 3. Running stage 2 meQTL analysis, whereby the pooled associations from all cohorts are retested in each cohort. 
Type Of Material Data handling & control 
Year Produced 2015 
Provided To Others? Yes  
Impact We have already recruited 30+ cohorts around the world and a sample size of more than 25,000 samples. Using the repository, all samples will be processed in a harmonized way. Through meta-analysis of summary statistics across all contributing cohorts, we have the potential to find many more trans methQTLs and explain more of the genetic variation underlying methylation variation than any study so far. 
URL https://github.com/MRCIEU/godmc
 
Title Identification of differentially methylated regions 
Description This software tool improves on previous work by properly controlling false positive rates, providing support for meta-analysis and increasing statistical power 
Type Of Material Data analysis technique 
Year Produced 2019 
Provided To Others? Yes  
Impact None as yet 
 
Title Meffil 
Description It is an R package "Efficient algorithms for analyzing DNA methylation data" (meffil) (https://github.com/perishky/meffil) which is designed to conduct quality control and normalization of large-scale methylation datasets. Meffil also conducts epigenome wide association studies (EWAS) using four different methods. 
Type Of Material Computer model/algorithm 
Year Produced 2015 
Provided To Others? Yes  
Impact To meet the challenges of processing an ever-increasing volume of methylation data, analysis pipelines must be easy to use, efficient, flexible, and able to seamlessly detect and handle technical artifacts. We have developed a new R package called meffil - efficient algorithms for analyzing DNA methylation - which meet these requirements. Meffil provides quality control reports,  normalizes large-scale datasets and include an analysis pipeline for epigenome-wide association studies. Different datasets in physically different locations can be normalized together without sharing original raw data using a minimum of information. The package has been tested on a dataset of ~5000 samples and will be used to process all ~30 datasets of the Genetics of DNA Methylation Consortium . 
URL https://github.com/perishky/meffil
 
Description ALPHABET 
Organisation University College Dublin
Department School of Public Health, Physiotherapy and Population Science
Country Ireland 
Sector Academic/University 
PI Contribution I am a co-investigator on a ERA-HDHL (BBSRC) collaborative research project on the influence of early life nutrition on offspring health led by UCD. Our contribution includes collating multi-centre epigenetic data, running epigenome-wide association studies, meta-analyses and causal analysis methods.
Collaborator Contribution The partners in this collaboration contribute data from various large birth cohort studies and expertise in nutrition and other clinical disciplines
Impact No outputs to report
Start Year 2017
 
Description ENIGMA -Anorexia 
Organisation University of Dresden
Country Germany 
Sector Academic/University 
PI Contribution analysis of imaging phenotype in anorexia
Collaborator Contribution analysis of imaging phenotype in anorexia
Impact No output yet, but expected in 2017
Start Year 2016
 
Description European Bioinformatics Institute 
Organisation EMBL European Bioinformatics Institute (EMBL - EBI)
Country United Kingdom 
Sector Academic/University 
PI Contribution We bring epidemiological and causal analysis expertise to this collaboration as well as generating epigenomic data for use by colleagues at EBI.
Collaborator Contribution Bioinformatic expertise for the functional annotation of observed associations.
Impact EBI have been involved in ARIES and have more recently been closely involved in formulating large strategic funding applications. The outputs of this work are too early to report. This is a multi-disciplinary collaboration between epidemiologists and bioinformaticians.
Start Year 2013
 
Description GW4 
Organisation Cardiff University
Country United Kingdom 
Sector Academic/University 
PI Contribution The GW4 strategic alliance has established the GW4 Epigenetics Consortium which I instigated and brings complementary expertise from the 4 contributing Universitites together.We hosted a 2 day symposium and workshops and have subsequently secured and undertaken research activities around the use of CRISPR/Cas9 in epigenetics studies
Collaborator Contribution 2 day symposium and workshops. Epidemiology expertise.
Impact 2 day symposium and workshops. Further grant application to GW4 for research activities. This is a multi-disciplinary collaboration between epidemiologists, clinicians, experimental biologists, bioinformaticians and epigeneticists
Start Year 2014
 
Description GW4 
Organisation University of Bath
Country United Kingdom 
Sector Academic/University 
PI Contribution The GW4 strategic alliance has established the GW4 Epigenetics Consortium which I instigated and brings complementary expertise from the 4 contributing Universitites together.We hosted a 2 day symposium and workshops and have subsequently secured and undertaken research activities around the use of CRISPR/Cas9 in epigenetics studies
Collaborator Contribution 2 day symposium and workshops. Epidemiology expertise.
Impact 2 day symposium and workshops. Further grant application to GW4 for research activities. This is a multi-disciplinary collaboration between epidemiologists, clinicians, experimental biologists, bioinformaticians and epigeneticists
Start Year 2014
 
Description GW4 
Organisation University of Exeter
Country United Kingdom 
Sector Academic/University 
PI Contribution The GW4 strategic alliance has established the GW4 Epigenetics Consortium which I instigated and brings complementary expertise from the 4 contributing Universitites together.We hosted a 2 day symposium and workshops and have subsequently secured and undertaken research activities around the use of CRISPR/Cas9 in epigenetics studies
Collaborator Contribution 2 day symposium and workshops. Epidemiology expertise.
Impact 2 day symposium and workshops. Further grant application to GW4 for research activities. This is a multi-disciplinary collaboration between epidemiologists, clinicians, experimental biologists, bioinformaticians and epigeneticists
Start Year 2014
 
Description GoDMC: Genetics of DNA Methylation Consortium 
Organisation Austrian Academy of Sciences
Department Research Centre for Molecular Medicine
Country Austria 
Sector Academic/University 
PI Contribution We are currently leading the GoDMC consortium. The GoDMC consortium consists of five core groups (IEU, Kings College London, University of Exeter, Leiden University Medical Centre and Austrian Academy of Sciences) and we recruited 30+ cohorts to contribute to the GoDMC consortium. Matt Suderman and Josine Min have developed an R package "Efficient algorithms for analyzing DNA methylation data" (meffil) (https://github.com/perishky/meffil) which is designed to conduct quality control and normalization of large-scale methylation datasets. Meffil also conducts epigenome wide association studies (EWAS) using four different methods. In addition, Josine Min and Gibran Hemani have written a pipeline on github, which automates all analyses. Participating cohorts will download the pipeline and will follow instructions to run the pipeline.
Collaborator Contribution We have monthly calls with the core team to discuss analyses and there are weekly calls between analysts for technical issues. The core analysts are testing the pipeline on their cohorts externally.
Impact Software development: R package meffil and github pipeline for GoDMC analyses Disciplines: Genetic epidemiology, epigenetic epidemiology
Start Year 2013
 
Description GoDMC: Genetics of DNA Methylation Consortium 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution We are currently leading the GoDMC consortium. The GoDMC consortium consists of five core groups (IEU, Kings College London, University of Exeter, Leiden University Medical Centre and Austrian Academy of Sciences) and we recruited 30+ cohorts to contribute to the GoDMC consortium. Matt Suderman and Josine Min have developed an R package "Efficient algorithms for analyzing DNA methylation data" (meffil) (https://github.com/perishky/meffil) which is designed to conduct quality control and normalization of large-scale methylation datasets. Meffil also conducts epigenome wide association studies (EWAS) using four different methods. In addition, Josine Min and Gibran Hemani have written a pipeline on github, which automates all analyses. Participating cohorts will download the pipeline and will follow instructions to run the pipeline.
Collaborator Contribution We have monthly calls with the core team to discuss analyses and there are weekly calls between analysts for technical issues. The core analysts are testing the pipeline on their cohorts externally.
Impact Software development: R package meffil and github pipeline for GoDMC analyses Disciplines: Genetic epidemiology, epigenetic epidemiology
Start Year 2013
 
Description GoDMC: Genetics of DNA Methylation Consortium 
Organisation Leiden University Medical Center
Country Netherlands 
Sector Multiple 
PI Contribution We are currently leading the GoDMC consortium. The GoDMC consortium consists of five core groups (IEU, Kings College London, University of Exeter, Leiden University Medical Centre and Austrian Academy of Sciences) and we recruited 30+ cohorts to contribute to the GoDMC consortium. Matt Suderman and Josine Min have developed an R package "Efficient algorithms for analyzing DNA methylation data" (meffil) (https://github.com/perishky/meffil) which is designed to conduct quality control and normalization of large-scale methylation datasets. Meffil also conducts epigenome wide association studies (EWAS) using four different methods. In addition, Josine Min and Gibran Hemani have written a pipeline on github, which automates all analyses. Participating cohorts will download the pipeline and will follow instructions to run the pipeline.
Collaborator Contribution We have monthly calls with the core team to discuss analyses and there are weekly calls between analysts for technical issues. The core analysts are testing the pipeline on their cohorts externally.
Impact Software development: R package meffil and github pipeline for GoDMC analyses Disciplines: Genetic epidemiology, epigenetic epidemiology
Start Year 2013
 
Description GoDMC: Genetics of DNA Methylation Consortium 
Organisation University of Exeter
Department Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution We are currently leading the GoDMC consortium. The GoDMC consortium consists of five core groups (IEU, Kings College London, University of Exeter, Leiden University Medical Centre and Austrian Academy of Sciences) and we recruited 30+ cohorts to contribute to the GoDMC consortium. Matt Suderman and Josine Min have developed an R package "Efficient algorithms for analyzing DNA methylation data" (meffil) (https://github.com/perishky/meffil) which is designed to conduct quality control and normalization of large-scale methylation datasets. Meffil also conducts epigenome wide association studies (EWAS) using four different methods. In addition, Josine Min and Gibran Hemani have written a pipeline on github, which automates all analyses. Participating cohorts will download the pipeline and will follow instructions to run the pipeline.
Collaborator Contribution We have monthly calls with the core team to discuss analyses and there are weekly calls between analysts for technical issues. The core analysts are testing the pipeline on their cohorts externally.
Impact Software development: R package meffil and github pipeline for GoDMC analyses Disciplines: Genetic epidemiology, epigenetic epidemiology
Start Year 2013
 
Description Institute of Metabolic Science, Cambridge 
Organisation University of Cambridge
Department Institute of Metabolic Science (IMS)
Country United Kingdom 
Sector Academic/University 
PI Contribution This long-standing collaboration focuses on complementary approaches to the developmental origins of adult disease with the group of Prof Sue Ozanne. My team bring epidemiological expertise, causal analysis methods, population epigenetics and leadership of the ARIES project.
Collaborator Contribution Dr Sue Ozanne brings expertise in animal model studies.
Impact Joint publication; Relton CL, Gaunt T, McArdle W, Ho K, Duggirala A, Shihab H, Woodward G, Lyttleton O, Evans DM, Reik W, Paul YL, Ficz G, Ozanne SE, Wipat A, Flanagan K, Lister A, Heijmans BT, Ring SM, Davey Smith G. Data Resource Profile: Accessible Resource for Integrated Epigenomic Studies (ARIES). Int J Epidemiol 2015;44(4):1181-90. PMID: 25991711
Start Year 2013
 
Description Leiden University Medical Centre 
Organisation Leiden University Medical Center
Country Netherlands 
Sector Multiple 
PI Contribution We have collaborated on the ARIES study which included the profiling of DNA methylation in autopsy samples provided by Dr Bas Heijman's group at LUMC in our Bristol labs. We have cleaned and QC'd the data and contributed to data analysis. We also work closely with this group in leading the Genetics of DNA Methylation Consortium (GoDMC).
Collaborator Contribution Our collaborators provided autopsy biological samples and associated data. They have led the data analysis and preparation of findings for publication.
Impact A Data Resource Profile has been published; Relton CL, Gaunt T, McArdle W, Ho K, Duggirala A, Shihab H, Woodward G, Lyttleton O, Evans DM, Reik W, Paul YL, Ficz G, Ozanne SE, Wipat A, Flanagan K, Lister A, Heijmans BT, Ring SM, Davey Smith G. Data Resource Profile: Accessible Resource for Integrated Epigenomic Studies (ARIES). Int J Epidemiol 2015;44(4):1181-90. PMID: 25991711 A further publication describing methylation profiles in different tissues is in preparation.
Start Year 2013
 
Description MRC The Gambia 
Organisation Medical Research Council (MRC)
Department MRC Unit, The Gambia
Country Gambia 
Sector Public 
PI Contribution Collaboration in epigenetics research. Co-investigator on recently funded award to establish a W African Bioresource in nutritional genetics and epigenetics.
Collaborator Contribution Myself and members of my team have committed to helping our colleagues at the MRC Gambia Unit establish a bioresource to support molecular epidemiology research in the future. This will involve researcher exchanges,workshops and training in Bristol and the provision of ongoing support and capacity building in The Gambia.
Impact No outputs to report as yet
Start Year 2018
 
Description School of Computing Science, Newcastle 
Organisation Newcastle University
Department School of Computing Science
Country United Kingdom 
Sector Academic/University 
PI Contribution This collaboration formed a central part of the development of infomatics systems for the ARIES (ALSPAC) project. Our role in the collaboration was as project leaders and to provide data and design guidance for the web browser that was ultimately produced for this project.
Collaborator Contribution Prof Anil Wipat's team provided expertise in data integration and helped to design and construct the ARIES-Explorer web interface.
Impact A description of the resource has been published; Relton CL, Gaunt T, McArdle W, Ho K, Duggirala A, Shihab H, Woodward G, Lyttleton O, Evans DM, Reik W, Paul YL, Ficz G, Ozanne SE, Wipat A, Flanagan K, Lister A, Heijmans BT, Ring SM, Davey Smith G. Data Resource Profile: Accessible Resource for Integrated Epigenomic Studies (ARIES). Int J Epidemiol 2015;44(4):1181-90. PMID: 25991711 A web-interface to browse summary data (see above URL)
Start Year 2013
 
Title EWAS Catalog 
Description This webtool/application has curated all published epigenome-wide association studies (EWAS) (using the Illumina BeadChip platform) and incorporated them in to a searchable data base. This allows the user to locate any variable methylation probes they may be interested in in a similar way to the GWAS catalog for genetic variants. It provides a centralised repository and search tool for any investigator interested in EWAS. 
Type Of Technology Webtool/Application 
Year Produced 2018 
Open Source License? Yes  
Impact The web application has just been released. It should have considerable impact across the research community as a browsing facility for all documented EWAS that appear in the published literature. 
URL http://www.ewascatalog.org
 
Description BBSRC Industry Showcase Event, Manchester 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Dissemination of information followed by questions and discussion

Engagement with industry
Year(s) Of Engagement Activity 2012
 
Description BiogenIdec, Cambridge, MA, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Dissemination of information followed by questions and discussion

Collaborative work discussed
Year(s) Of Engagement Activity 2011
 
Description Centre for Cardiovascular Sciences, University of Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar: Dissemination of information followed by questions and discussion

Collaboration and plans discussed for future action
Year(s) Of Engagement Activity 2012
 
Description Columbia University, New York, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar - dissemination of information followed by questions and discussion

Consolidated collaborative links
Year(s) Of Engagement Activity 2011
 
Description Department of Dermatology, Institute of Cellular Medicine, Newcastle University 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar: Dissemination of information followed by questions and discussion

Increase in awareness, change of views, opinions and behaviours noted
Year(s) Of Engagement Activity 2012
 
Description Epigenomics and Complex Disease Conference, Cambridge 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Plenary Session - dissemination of information and stimulation of discussion

Effective Networking
Year(s) Of Engagement Activity 2011
 
Description European Atherosclerosis Society, Copenhagen, Denmark 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Lecture - Genetics and Epidemiology of Cardiovascular Disease

Stimulation of discussion - dissemination of information - questions and answers
Year(s) Of Engagement Activity 2011
 
Description European Society for Paediatric Research, Newcastle 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Plenary Session - dissemination of information, stimulate discussion

Dissemination to a largely clinical audience
Year(s) Of Engagement Activity 2011
 
Description Harvard School of Public Health 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited Speaker: Seminar: Harvard School of Public Health, Boston, USA, January 2014

Informed debate and discussion
Year(s) Of Engagement Activity 2014
 
Description Health Sciences Center, University of Colorado Denver, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar: Dissemination of information followed by questions and discussion

Future plans for collaboration discussed
Year(s) Of Engagement Activity 2013
 
Description Hidden Influences on Health Across the Life Course 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Paper Presentation
Geographic Reach National
Primary Audience Health professionals
Results and Impact Seminar at University of Durham June 2013 - Hidden Influences on Health Across the LIfe Course

Informed discussion
Year(s) Of Engagement Activity 2013
 
Description Hot Topics: Developments in Epigenetics, Adelaide, Australia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar: Dissemination of information followed by questions and discussion

Extensive discussion of methodology
Year(s) Of Engagement Activity 2013
 
Description Keystone Symposium Boston USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Invited Speaker: Keystone Symposium: Epigenetic Programme and Inheritance, Boston, USA April 2014

Dissemination of information and discussion
Year(s) Of Engagement Activity 2014
 
Description MRC Toxicology Unit, University of Leicester 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar - dissemination of information followed by questions and discussion

Constructive inter-MRC Unit links made
Year(s) Of Engagement Activity 2012
 
Description Merck, Rahway, New Jersey, USA 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Dissemination of information followed by questions and discussion

Collaboration discussed
Year(s) Of Engagement Activity 2011
 
Description NIHR-BRC Geneomics Workshop, Newcastle University 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach National
Primary Audience Health professionals
Results and Impact NIHR-BRC Genomics Workshop, Newcastle University, 18th July 2013

Informed debate and discussion.
Year(s) Of Engagement Activity 2013
 
Description Nanjing Medical University, Nanjing - GEoCoDE Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Dissemination of information followed by questions and discussion

Staff exchanges and collaboration planned
Year(s) Of Engagement Activity 2011
 
Description Osteoporosis and Bone Conference, Manchester 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Lecture: dissemination of information followed by questions and discussion

Collaboration formed
Year(s) Of Engagement Activity 2012
 
Description Population Health: Past, Present and Future 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Dissemination of information and discussioin

Invited Speaker: Population Health: Past, Present and Future. University of Michigan, Ann Arbor, USA, April 2014
Year(s) Of Engagement Activity 2014
 
Description Queensland Institute of Medical Research, Brisbane, Australia - GEoCoDE Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar: Dissemination of information followed by questions and discussion

Collaboration initiated
Year(s) Of Engagement Activity 2013
 
Description Robinson Institute, Adelaide, Australia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Plenary: Dissemination of information followed by questions and discussion

Advice exchanged and new projects discussed
Year(s) Of Engagement Activity 2013
 
Description School of Social and Community Medicine, University of Bristol 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar - dissemination of information followed by questions and discussion

Encouraged vibrant discussion of methods and issues
Year(s) Of Engagement Activity 2012
 
Description South Asia Network for Chronic Diseases, New Delhi 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar: dissemination of information followed by questions and discussion

Grants submitted subsequently
Year(s) Of Engagement Activity 2012
 
Description UK Environmental Mutagens Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Lecture: UK Environmental Mutagens Society, Newcastle University, December 2013

Informed discussion and debate
Year(s) Of Engagement Activity 2008,2013
 
Description University of Adelaide, Australia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar: Dissemination of information followed by questions and discussion

Increased awareness of important issues in epigenetic epidemiology
Year(s) Of Engagement Activity 2013
 
Description University of Cape Town - GEoCoDE Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Dissemination of information followed by questions and discussion

Staff exchanges and collaboration planned
Year(s) Of Engagement Activity 2011
 
Description University of Chicago - Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Dissemination of information followed by questions and discussion : The Role of Genetic and Environmental Factors Across the Lifecourse: Improving the Rigour of Causal Inference

Interaction with a multi-disciplinary audience, including econoists and social scientists
Year(s) Of Engagement Activity 2011
 
Description University of Pelotas, Brazil 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Seminar : Dissemination of information followed by questions and discussion

Fuelled future grant applications and research activity
Year(s) Of Engagement Activity 2011
 
Description University of Witwatersrand - GEoCoDE Programme 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Dissemination of information followed by questions and discussion

Staff exchanges and collaboration planned
Year(s) Of Engagement Activity 2011
 
Description WUN Public Health Conference, Shanghai 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Informed debate followed by questions and discussion

Stimulation of thinking and discussion. No known notable impacts
Year(s) Of Engagement Activity 2011
 
Description Why We Are Who We Are, They Hay-on-Wye Philosophy Festival 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact The Hay-on-Wye Philosophy Festival : Why We Are Who We Are : Dissemination of information and questions

Lively discussion and debate on current perceptions in epigenetics
Year(s) Of Engagement Activity 2013
 
Description World Congress in Epidemiology, Anchorage, Alaska 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Dissemination of information and discussion

Invited Speaker: World Congress of Epidemiology, Anchorage, Alaska, USA, August 2014
Year(s) Of Engagement Activity 2014