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Genome-wide association studies (GWAS) have traditionally been undertaken in homogeneous populations from the same ancestry group. However, with the increasing availability of GWAS in large-scale multi-ethnic cohorts, we have evaluated a framework for detecting association of genetic variants with complex traits, allowing for population structure, and developed a powerful test of heterogeneity in allelic effects between ancestry groups. We have applied the methodology to identify and characterise loci associated with susceptibility to type 2 diabetes (T2D) using GWAS data from the Resource for Genetic Epidemiology on Adult Health and Aging, a large multi-ethnic population-based cohort, created for investigating the genetic and environmental basis of age-related diseases. We identified a novel locus for T2D susceptibility at genome-wide significance (P<5 × 10(-8)) that maps to TOMM40-APOE, a region previously implicated in lipid metabolism and Alzheimer's disease. We have also confirmed previous reports that single-nucleotide polymorphisms at the TCF7L2 locus demonstrate the greatest extent of heterogeneity in allelic effects between ethnic groups, with the lowest risk observed in populations of East Asian ancestry.

Original publication

DOI

10.1038/ejhg.2016.17

Type

Journal article

Journal

Eur J Hum Genet

Publication Date

08/2016

Volume

24

Pages

1175 - 1180

Keywords

Apolipoproteins E, Asian Continental Ancestry Group, Diabetes Mellitus, Type 2, Genetic Loci, Genome-Wide Association Study, Humans, Membrane Transport Proteins, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein