EPIC-InterAct is the world’s largest study of incident Type 2 Diabetes (T2DM) established as a case-cohort study nested within the pan-European EPIC study which has amassed 4 million person years of follow-up. Led by the MRC Epidemiology Unit and initially funded by an EU FP6 grant, we have ascertained 12,403 incident cases of T2DM in 8 European countries and created a random sub-cohort of 16,835 individuals. The study has also enabled in-depth characterisation of the prospective associations of a wide range of lifestyle and genetic factors with type 2 diabetes, a vital pre-requisite to studying interactions.
More than 60 papers have been published based on results from EPIC-InterAct, with more than 20 working groups currently active in using the data to address different research questions. Funding has been secured to obtain further detailed measurements on EPIC-InterAct participants. Our establishment of a random sub-cohort in EPIC has also enabled the study of other diseases including coronary heart disease (EPIC-Heart), stroke (EPIC-CVD), Parkinsons disease and Alzheimers.
The overall aims of the EPIC-InterAct project are to discover how genes interact with potentially modifiable lifestyle and behavioural factors in their influence on the incidence of type 2 diabetes, and to inform strategies for prevention. The core EPIC-InterAct study is a large prospective case-cohort study of incident type 2 diabetes nested within the EPIC (European Prospective Investigation into Cancer and Nutrition) cohort study initiated in the late 1980s. It includes 12,403 verified incident cases of type 2 diabetes, and a random sub-cohort of 16,835 individuals. Data come from 26 centres within 8 European countries. Data are available for EPIC-InterAct participants on a wide range of variables at baseline, including measures of anthropometry, information on socioeconomic status, education level and ethnicity, measures of dietary intake collected by self- or interview-administered dietary questionnaires developed and validated within each country, and a validated 4 category index of physical activity derived from a questionnaire covering occupational and recreational activity. Genomewide data have been obtained for all participants using a combination of the Illumina 660W-Quad Bead and HumanCore Exome chips. A high-throughput laboratory analysis method has been developed by the project which has enabled the measurement of 37 plasma phospholipid fatty acids. Twenty-one biomarkers in serum samples and HbA1c in erythrocyte samples have been measured. Further data are currently being generated on vitamin D, C, and carotenoids.
So far the project has produced more than 60 publications, including contributing to at least 8 collaborative meta-analyses. There are more than 20 working groups actively engaged in ongoing analyses of EPIC-InterAct data. The synergistic benefits of the case-cohort design are being realised with the extensive use of EPIC-InterAct sub-cohort data by the EPIC-CVD, EPIC-Heart and EPIC-Parkinson’s Disease projects. The design of EPIC-CVD and EPIC-Heart, which are led by Professor John Danesh (University of Cambridge) and funded by grants from the MRC/BHF and EU FP7 programme, has mirrored that of EPIC-InterAct; these studies have ascertained approx. 15,000 coronary heart disease events and 12,000 cerebrovascular events, and working groups are currently being established.
The EPIC-InterAct project is coordinated by a management team based at the MRC Epidemiology Unit, led by Nick Wareham, who is also a member of the EPIC steering committee which oversees all uses of EPIC data. The EPIC-InterAct management team reviews all proposals from working groups of EPIC-InterAct partners to use the data, and publications which arise from their work. The management of study proposals, analyses and publications is co-ordinated through a bespoke on-line system developed by the Unit. The Unit is responsible for sample management related activities, co-ordination of biochemistry provision, genetic laboratory work, managing EPIC-InterAct data, preparing data releases, coordination of and advising on statistical analyses, and provision of results from EPIC-InterAct to various other research consortia. As well as making the sub-cohort data available for use by the EPIC-CVD and EPIC-Heart projects, within these projects Nick Wareham leads a Research Line on nutritional biomarkers, Nita Forouhi leads a Work Package on fatty acids, and Nicola Kerrison and Stephen Sharp provide extensive advice on data management and statistical issues.
The set-up of the EPIC-InterAct project was originally funded by a grant from the EU FP6 programme (2006-2011). Funding to obtain additional measurements on EPIC-InterAct participants has been provided by the MRC Cambridge Initiative in Obesity and Metabolic Diseases (2013-2018). MRC core funding has been used to fund telomere length measurements and HumanCore Exome chips. MRC core-funded individuals are responsible for the ongoing management of the project, specifically related to data management, statistical analysis, laboratory work and website management, as well as scientific leadership of the majority of the genetics and nutritional research being undertaken within the project.