Genetic susceptibility to type 2 diabetes and obesity: from genome-wide association studies to rare variants and beyond

Diabetologia. 2014 Aug;57(8):1528-41. doi: 10.1007/s00125-014-3270-4. Epub 2014 May 24.


During the past 7 years, genome-wide association studies have shed light on the contribution of common genomic variants to the genetic architecture of type 2 diabetes, obesity and related intermediate phenotypes. The discoveries have firmly established more than 175 genomic loci associated with these phenotypes. Despite the tight correlation between type 2 diabetes and obesity, these conditions do not appear to share a common genetic background, since they have few genetic risk loci in common. The recent genetic discoveries do however highlight specific details of the interplay between the pathogenesis of type 2 diabetes, insulin resistance and obesity. The focus is currently shifting towards investigations of data from targeted array-based genotyping and exome and genome sequencing to study the individual and combined effect of low-frequency and rare variants in metabolic disease. Here we review recent progress as regards the concepts, methodologies and derived outcomes of studies of the genetics of type 2 diabetes and obesity, and discuss avenues to be investigated in the future within this research field.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / genetics*
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genetic Variation*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Insulin Resistance / genetics*
  • Obesity / genetics*