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Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank.


ABSTRACT: AIMS/HYPOTHESIS:Genome-wide association studies (GWAS) have discovered many risk variants for type 2 diabetes. However, estimates of the contributions of risk variants to type 2 diabetes predisposition are often based on highly selected case-control samples, and reliable estimates of population-level effect sizes are missing, especially in non-European populations. METHODS:The individual and cumulative effects of 59 established type 2 diabetes risk loci were measured in a population-based China Kadoorie Biobank (CKB) study of 93,000 Chinese adults, including >7,100 diabetes cases. RESULTS:Association signals were directionally consistent between CKB and the original discovery GWAS: of 56 variants passing quality control, 48 showed the same direction of effect (binomial test, p?=?2.3?×?10(-8)). We observed a consistent overall trend towards lower risk variant effect sizes in CKB than in case-control samples of GWAS meta-analyses (mean 19-22% decrease in log odds, p???0.0048), likely to reflect correction of both 'winner's curse' and spectrum bias effects. The association with risk of diabetes of a genetic risk score, based on lead variants at 25 loci considered to act through beta cell function, demonstrated significant interactions with several measures of adiposity (BMI, waist circumference [WC], WHR and percentage body fat [PBF]; all p interaction?

SUBMITTER: Gan W 

PROVIDER: S-EPMC4901105 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank.

Gan Wei W   Walters Robin G RG   Holmes Michael V MV   Bragg Fiona F   Millwood Iona Y IY   Banasik Karina K   Chen Yiping Y   Du Huaidong H   Iona Andri A   Mahajan Anubha A   Yang Ling L   Bian Zheng Z   Guo Yu Y   Clarke Robert J RJ   Li Liming L   McCarthy Mark I MI   Chen Zhengming Z  

Diabetologia 20160406 7


<h4>Aims/hypothesis</h4>Genome-wide association studies (GWAS) have discovered many risk variants for type 2 diabetes. However, estimates of the contributions of risk variants to type 2 diabetes predisposition are often based on highly selected case-control samples, and reliable estimates of population-level effect sizes are missing, especially in non-European populations.<h4>Methods</h4>The individual and cumulative effects of 59 established type 2 diabetes risk loci were measured in a populati  ...[more]

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