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Open Access 01-07-2016 | Article

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

Authors: 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, Zhengming Chen, on behalf of the China Kadoorie Biobank Collaborative Group

Published in: Diabetologia | Issue 7/2016

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 < 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.

Available only for authorised users

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Title: Evaluation of type 2 diabetes genetic risk variants in Chinese adults: findings from 93,000 individuals from the China Kadoorie Biobank
Authors: 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
Zhengming Chen
on behalf of the China Kadoorie Biobank Collaborative Group
Publication date: 01-07-2016
Publisher: Springer Berlin Heidelberg
Published in: Diabetologia / Issue 7/2016
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-3920-9

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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

Methods

Results

Conclusions/interpretation

Access to research materials

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Abstract

Aims/hypothesis

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Conclusions/interpretation

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