Transferability across ethnic groups

Abstract

Type 2 diabetes (T2D) is a common complex disease increasing in prevalence worldwide. While studies in populations of European ancestry predominated early gene discovery efforts, extension of genome-wide association studies (GWAS) to multiple ethnic groups has identified additional novel loci and insights based on differences in allele frequency, physiologic effect, and evolutionary history between populations. These studies highlight the value of global genetic studies in diverse populations. Transferability studies of T2D, and to a limited extent related traits, are now under way across diverse ethnic groups and have revealed (a) consistent effects for several T2D loci across most ethnic groups implying shared underlying causal variants; (b) allelic heterogeneity at several loci, validating a critical role for these loci in disease risk; (c) the utility of studies in different ethnic groups, especially of those with recent African ancestry, in fine mapping of genetic associations based on regional differences in linkage disequilibrium (LD); (d) heterogeneity of effect between ethnic groups at some T2D loci; and (e) population-specific effects. Discovery and transferability studies across ethnic groups promise to be integral in advancing our understanding of the genetic basis of T2D and providing insights into differences in prevalence and physiology of disease between ethnic groups. Multiethnic genetic studies for T2D are critical for addressing health disparities and developing preventive and therapeutic strategies to reduce disease burden.