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

Gan W., Walters RG., Holmes MV., Bragg F., Millwood IY., Banasik K., Chen Y., Du H., Iona A., Mahajan A., Yang L., Bian Z., Guo Y., Clarke RJ., Li L., McCarthy MI., Chen Z., China Kadoorie Biobank Collaborative Group None.

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 

DOI

10.1007/s00125-016-3920-9

Type

Journal article

Journal

Diabetologia

Publication Date

07/2016

Volume

59

Pages

1446 - 1457

Keywords

Biobank, Chinese, Genetic risk score, Population-based cohort studies, Type 2 diabetes, Winner’s curse, Adult, Asian Continental Ancestry Group, Biological Specimen Banks, China, Diabetes Mellitus, Type 2, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Waist Circumference

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