General summary
Aim
The InterAct consortium will construct a case-control study nested
within an existing large cohort - the EPIC study. The cohort for this
project is large, comprising 350,000 participants from 8 European
countries. Standardised dietary and physical activity information is
available at baseline, and there is an available DNA source and plasma
for nutritional biomarkers. Follow up has been completed for an average
of 8 years. The collaborators will amass a case set of 10,000
individuals and a similarly sized control cohort free of diabetes at
baseline and during follow-up. DNA extraction and genotyping will be
undertaken using centralised high throughput methods. The choice of
polymorphisms in candidate genes will be undertaken by a group leading
efforts to discover diabetes genes through a variety of approaches
including whole genome association studies. The causal inference from
the discovery of gene-lifestyle interactions will be strengthened by
testing the same genes in existing intervention trials, which have
examined the effectiveness of lifestyle changes on diabetes incidence.
These include the Finnish Diabetes Prevention Study, the Danish Inter99
project and the Indian Diabetes Prevention Study. The demonstration of
differential response to lifestyle change by genotype will not only
provide greater aetiologic understanding, but will also present the
opportunity to investigate possibilities to use genotypic data in risk
stratification and identification of individuals who have the potential
to benefit most from targeted lifestyle prevention.
The objectives of the InterAct Project will be met by 4 research lines.
Analysis of gene-lifestyle interaction in observational studies of diabetes incidence
Aim: to construct a nested case-control study for type 2 diabetes
within the EPIC observational cohort and to use this study as the basis
for studying gene-lifestyle interaction.
Analysis of nutritional factors and physical activity in observational studies of diabetes incidence
Aim: to study the association of nutritional, dietary and physical activity behaviours with incident diabetes in the nested case-control study and to contribute to the analysis of gene-lifestyle interaction.
Analysis of genetic factors in observational studies of diabetes incidence
Aim: to study the association of genetic variation with incident diabetes in the nested case-control study and to contribute to the analysis of main genetic effects and gene-lifestyle interaction.
Analysis of gene-lifestyle interaction in intervention studies