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General summary


The InterAct consortium has constructed a case-cohort study nested within the existing large cohort ‘EPIC’ study.  The EPIC study includes 350,000 participants across 10 European countries.  A key strength of this design is that standardised dietary and physical activity information was collected across the countries providing baseline data for participants, together with DNA samples which have been extracted and genotyped and plasma samples which have been analysed for nutritional biomarkers.


Participants were followed up for on average 8 years, providing 4 million ‘person years’.  During this time a total of 12,403 individuals were identified as having developed type 2 diabetes.  InterAct has also defined a subcohort of 16,154 controls who were free of diabetes at baseline.


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. This demonstration of differential response to lifestyle change by genotype will not only provide greater aetiologic understanding, but can 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 InterAct Project was divided into 4 research lines:


  • Set up a nested case-cohort study for the analysis of gene-lifestyle interaction in observational studies of diabetes incidence.
  • Analysis of nutritional factors and physical activity to study the association of nutritional, dietary and physical activity behaviours with incident diabetes in the nested case-cohort study and to contribute to the analysis of gene-lifestyle interaction.
  • Analysis of genetic factors to study the association of genetic variation with incident diabetes in the nested case-cohort study and to contribute to the analysis of main genetic effects and gene-lifestyle interaction.
  • Analysis of gene-lifestyle interaction to construct a consortium of lifestyle intervention diabetes prevention trials in order to study the association of the genetic variation with differential response to the lifestyle intervention and to consider the implications of these findings for preventive action.