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Genome-wide association study of alcohol dependence in male Han Chinese and cross-ethnic polygenic risk score comparison
- Source :
- Translational Psychiatry, Translational Psychiatry, Vol 9, Iss 1, Pp 1-10 (2019)
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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.
- Subjects :
- Adult
Cross-Cultural Comparison
Male
China
Multifactorial Inheritance
Ethnic group
Addiction
Genome-wide association study
Polymorphism, Single Nucleotide
White People
Article
lcsh:RC321-571
Young Adult
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Barratt Impulsiveness Scale
Asian People
Humans
Medicine
SNP
Genetic Predisposition to Disease
lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry
Biological Psychiatry
030304 developmental biology
0303 health sciences
business.industry
Aldehyde Dehydrogenase, Mitochondrial
Comparative genomics
Alcohol dependence
Alcohol Dehydrogenase
ADH1B
Middle Aged
Michigan Alcoholism Screening Test
3. Good health
Black or African American
Alcoholism
Psychiatry and Mental health
Logistic Models
Case-Control Studies
Cohort
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Demography
Subjects
Details
- ISSN :
- 21583188
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Translational Psychiatry
- Accession number :
- edsair.doi.dedup.....07b7b5e6463e221fdf23b13d0793007b