Type 2 diabetes: unravelling the interaction between genetic predisposition and lifestyle

Abstract

The high concordance rate of type 2 diabetes in monozygotic twins, the increased risk of diabetes in the offspring of affected parents and the difference in the prevalence of diabetes between various ethnic groups suggest a high heritability for this disorder [1]. On the other hand, modern societies are characterised by intense urbanisation, which is linked to tremendous environmental and behavioural changes: physical inactivity, an energy-dense diet, psychosocial stress and exposure to environmental pollutants [1–3]. The descriptive epidemiology of type 2 diabetes suggests that the interaction between genetic susceptibility and these modern lifestyle factors, as well as environmental risk factors, is critical to the development of the disease [1]. Current case–control studies have succeeded in identifying dozens of novel risk variants (see Herder and Roden [1] and the references therein), but have failed to explain most of the expected genetic contribution to the risk of type 2 diabetes [4]. Thus, there is a need for additional study designs to address the issue of ‘missing heritability’. This missing heritability might at least partly be due to the presently unknown modifying effect of lifestyle factors, and therefore adequately powered epidemiological studies to investigate gene–lifestyle interaction in the prediction of type 2 diabetes are both timely and welcome [5]. A major challenge is that dietary patterns and physical activity are not easy to assess in epidemiological studies [6]. Although a number of scientific consortia have been established to undertake meta-analyses of genetic data from loci associated with type 2 diabetes, different definitions and measurements of diet and physical activity hamper the pooling of such data to investigate gene–lifestyle interactions [1, 6]. The study of these complex and multidimensional behaviours ideally requires protocols in which the standardisation of instruments has already been implemented at the design stage [7]. The European Prospective Investigation into Cancer and Nutrition (EPIC) was initiated in the late 1980s and involved standardised baseline information on lifestyle behaviours [8]. The goal of the InterAct consortium is to carry out a meta-analysis of gene–lifestyle interactions in terms of the risk of type 2 diabetes based on EPIC cohorts from eight European countries [9].