Details

Autor(en) / Beteiligte

• Gan, Wei
• Walters, Robin G.
• Holmes, Michael V.
• Bragg, Fiona
• Millwood, Iona Y.
• Banasik, Karina
• Chen, Yiping
• Du, Huaidong
• Iona, Andri
• Mahajan, Anubha
• Yang, Ling
• Bian, Zheng
• Guo, Yu
• Clarke, Robert J.
• Li, Liming
• McCarthy, Mark I.
• Chen, Zhengming

Titel

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

Ist Teil von

• Diabetologia, 2016-07, Vol.59 (7), p.1446-1457

Ort / Verlag

Berlin/Heidelberg: Springer Berlin Heidelberg

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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  < 1 × 10 −4 ), with a greater effect being observed in leaner adults. Conclusions/interpretation Our study provides further evidence of shared genetic architecture for type 2 diabetes between Europeans and East Asians. It also indicates that even very large GWAS meta-analyses may be vulnerable to substantial inflation of effect size estimates, compared with those observed in large-scale population-based cohort studies. Access to research materials Details of how to access China Kadoorie Biobank data and details of the data release schedule are available from www.ckbiobank.org/site/Data+Access .