Dataset Information

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 < 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 .

SUBMITTER: Gan W

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

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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]

PMID: 27053236

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Project description:AimsTo assess the associations of problem drinking with wellbeing and mortality in Chinese men.DesignPopulation-based prospective cohort study.SettingTen diverse areas across China.ParticipantsA total of 210 259 men aged 30-79 years enrolled into China Kadoorie Biobank between 2004 and 2008.MeasurementsSelf-reported alcohol intake and indicators of problem drinking (i.e. drinking in the morning, unable to stop drinking, unable to work due to drinking, negative emotions after drinking, having shakes after stopping drinking) were assessed by questionnaire at baseline, along with stressful life events (e.g. divorce, income loss, violence) and wellbeing-related measures (e.g. life satisfaction, sleep problems, depression, anxiety). Problem drinking was defined as reporting at least one of the drinking problem indicators. Follow-up for mortality and hospitalized events was through linkage to death registries and national health insurance systems. Multivariate logistic regression models assessed cross-sectional relationships between problem drinking and stressful life events/wellbeing. Cox proportional hazards regression models estimated prospective associations of problem drinking with mortality/hospitalized events.FindingsA third of men were current regular drinkers (i.e. drank alcohol at least weekly), 24% of whom reported problem drinking: 8% of all men. Experience of stressful life events in the past 2 years, especially income loss [odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.45-2.39], was associated with increased problem drinking. Compared with low-risk drinkers (i.e. intake < 200 g/week, no reported problem drinking or habitual heavy drinking episodes), men with problem drinking had poorer self-reported health, poorer life satisfaction and sleep problems, and were more likely to have symptoms of depression and anxiety. Men with two or more problem drinking indicators had an approximately twofold higher risk for all-cause mortality as well as mortality and morbidity from external causes (i.e. injuries), respectively, and 15% higher risk for any hospitalization, compared with low-risk drinkers (all P < 0.01).ConclusionEight per cent of men in China are problem drinkers, and this is associated with significantly increased risk of physical and mental health problems and premature death.

Dataset Information

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

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Access to research materials

Publications

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

Similar Datasets

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