Dataset Information

Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.

ABSTRACT: Alcohol-related behaviors are moderately heritable and have ethnic-specific characteristics. At present, genetic studies for alcohol dependence (AD) in Chinese populations are underrepresented. We are the first to conduct a genome-wide association study (GWAS) for AD using 533 male alcoholics and 2848 controls of Han Chinese ethnicity and replicate our findings in 146 male alcoholics and 200 male controls. We then assessed genetic effects on AD characteristics (drinking volume/age onset/Michigan Alcoholism Screening Test (MAST)/Barratt Impulsiveness Scale (BIS-11)), and compared the polygenic risk of AD in Han Chinese with other populations (Thai, European American and African American). We found and validated two significant loci, one located in 4q23, with lead SNP rs2075633*ADH1B (Pdiscovery?=?6.64?×?10-16) and functional SNP rs1229984*ADH1B (Pdiscovery?=?3.93?×?10-13); and the other located in 12q24.12-12q24.13, with lead SNP rs11066001*BRAP (Pdiscovery?=?1.63?×?10-9) and functional SNP rs671*ALDH2 (Pdiscovery?=?3.44?×?10-9). ADH1B rs1229984 was associated with MAST, BIS_total score and average drinking volume. Polygenic risk scores from the Thai AD and European American AD GWAS were significantly associated with AD in Han Chinese, which were entirely due to the top two loci, however there was no significant prediction from African Americans. This is the first case-control AD GWAS in Han Chinese. Our findings demonstrate that these variants, which were highly linked with ALDH2 rs671 and ADH1B rs1229984, were significant modulators for AD in our Han Chinese cohort. A larger replication cohort is still needed to validate our findings.

SUBMITTER: Sun Y

PROVIDER: S-EPMC6779867 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.

Sun Yan Y Chang Suhua S Wang Fan F Sun Hongqiang H Ni Zhaojun Z Yue Weihua W Zhou Hang H Gelernter Joel J Malison Robert T RT Kalayasiri Rasmon R Wu Ping P Lu Lin L Shi Jie J

Translational psychiatry 20191007 1

Alcohol-related behaviors are moderately heritable and have ethnic-specific characteristics. At present, genetic studies for alcohol dependence (AD) in Chinese populations are underrepresented. We are the first to conduct a genome-wide association study (GWAS) for AD using 533 male alcoholics and 2848 controls of Han Chinese ethnicity and replicate our findings in 146 male alcoholics and 200 male controls. We then assessed genetic effects on AD characteristics (drinking volume/age onset/Michigan ...[more]

PMID: 31591379

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Project description:ImportanceMajor depressive disorder (MDD) and alcohol dependence (AD) are heritable disorders with significant public health burdens, and they are frequently comorbid. Common genetic factors that influence the co-occurrence of MDD and AD have been sought in family, twin, and adoption studies, and results to date have been promising but inconclusive.ObjectiveTo examine whether AD and MDD overlap genetically, using a polygenic score approach.Design, settings, and participantsAssociation analyses were conducted between MDD polygenic risk score (PRS) and AD case-control status in European ancestry samples from 4 independent genome-wide association study (GWAS) data sets: the Collaborative Study on the Genetics of Alcoholism (COGA); the Study of Addiction, Genetics, and Environment (SAGE); the Yale-Penn genetic study of substance dependence; and the National Health and Resilience in Veterans Study (NHRVS). Results from a meta-analysis of MDD (9240 patients with MDD and 9519 controls) from the Psychiatric Genomics Consortium were applied to calculate PRS at thresholds from P?<?.05 to P???.99 in each AD GWAS data set.Main outcomes and measuresAssociation between MDD PRS and AD.ResultsParticipants analyzed included 788 cases (548 [69.5%] men; mean [SD] age, 38.2 [10.8] years) and 522 controls (151 [28.9.%] men; age [SD], 43.9 [11.6] years) from COGA; 631 cases (333 [52.8%] men; age [SD], 35.0 [7.7] years) and 756 controls (260 [34.4%] male; age [SD] 36.1 [7.7] years) from SAGE; 2135 cases (1375 [64.4%] men; age [SD], 39.4 [11.5] years) and 350 controls (126 [36.0%] men; age [SD], 43.5 [13.9] years) from Yale-Penn; and 317 cases (295 [93.1%] men; age [SD], 59.1 [13.1] years) and 1719 controls (1545 [89.9%] men; age [SD], 64.5 [13.3] years) from NHRVS. Higher MDD PRS was associated with a significantly increased risk of AD in all samples (COGA: best P?=?1.7?×?10-6, R2?=?0.026; SAGE: best P?=?.001, R2?=?0.01; Yale-Penn: best P?=?.035, R2?=?0.0018; and NHRVS: best P?=?.004, R2?=?0.0074), with stronger evidence for association after meta-analysis of the 4 samples (best P?=?3.3?×?10-9). In analyses adjusted for MDD status in 3 AD GWAS data sets, similar patterns of association were observed (COGA: best P?=?7.6?×?10-6, R2?=?0.023; Yale-Penn: best P?=?.08, R2?=?0.0013; and NHRVS: best P?=?.006, R2?=?0.0072). After recalculating MDD PRS using MDD GWAS data sets without comorbid MDD-AD cases, significant evidence was observed for an association between the MDD PRS and AD in the meta-analysis of 3 GWAS AD samples without MDD cases (best P?=?.007).Conclusions and relevanceThese results suggest that shared genetic susceptibility contributes modestly to MDD and AD comorbidity. Individuals with elevated polygenic risk for MDD may also be at risk for AD.

Dataset Information

Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.

Publications

Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison.

Similar Datasets

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