The genetic and epigenetic basis of type 2 diabetes and obesity

Abstract

Type 2 diabetes (T2D) and obesity are complex disorders that constitute major public health problems. The evidence for familial aggregation of both T2D and obesity is substantial. To date, more than 150 genetic loci are associated with the development of monogenic, syndromic, or multifactorial forms of T2D or obesity. However, the proportion of overall trait variance explained by these associated loci is modest (~5-10% for T2D, ~2% for body mass index (BMI)). Some of the familial aggregation not attributable to known genetic variation, as well as many of the effects of environmental exposures, may reflect epigenetic processes. In this review, we discuss the evidence concerning the genetic contribution to individual risk of T2D and obesity, and explore the potential role of epigenetic mechanisms. We also explain how genetics, epigenetics, and environment are likely to interact to define the individual risk of disease.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declared no conflict of interest.

Figures

Figure 1

The complex relationship among genetics, epigenetics, and the environment in the susceptibility to type 2 diabetes (T2D) and obesity. The schematic Venn diagram illustrates the independent and interacting effects of genetics, epigenetics, and the environment that can give rise to T2D and obesity risk and familial aggregation. The diagram highlights where these effects overlap as well as where overlapping effects can either interact or appear as one of the others.

Figure 2

The relationship between risk of type 2 diabetes (T2D) and birth weight. The U-shaped relationship between T2D risk and birth weight is shown in this illustration (not to scale). Both genetic and nongenetic effects are listed on each side of the curve and refer to the upper tails of the curve at high T2D risk (shaded red).