title: Multi-ethnic genome-wide association study identifies novel locus for type 2 diabetes susceptibility.
abstract: 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.
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, UK.
authors.forename: James P
authors.initials: JP
authors.lastname: Cook
authors.affiliation: Department of Biostatistics, University of Liverpool, Liverpool, UK.|Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Morris
mesh_terms: D001057:Apolipoproteins E / Q000235:genetics; D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology / Q000235:genetics*; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D020641:Polymorphism, Single Nucleotide; D058118:Transcription Factor 7-Like 2 Protein / Q000235:genetics
chemical_list: C000612345:ApoE protein, human; D001057:Apolipoproteins E; D026901:Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; C544894:TCF7L2 protein, human; C400783:TOMM40 protein, human; D058118:Transcription Factor 7-Like 2 Protein