Kaempferol 3-sophoroside-7-rhamnoside

27053236

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 pinteraction < 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. Electronic supplementary material The online version of this article (doi:10.1007/s00125-016-3920-9) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Biobank, Chinese, Genetic risk score, Population-based cohort studies, Type 2 diabetes, Winner’s curse

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

Wei Gan, Robin G. Walters, Michael V. Holmes, Fiona Bragg, Iona Y. Millwood, Karina Banasik, Yiping Chen, Huaidong Du, Andri Iona, Anubha Mahajan, Ling Yang, Zheng Bian, Yu Guo, Robert J. Clarke, Liming Li, Mark I. McCarthy,corresponding author Zhengming Chen,corresponding author and on behalf of the China Kadoorie Biobank Collaborative Group

2016;