Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders

23andMe Research Team

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10 –13 ) and African ancestries (rs2066702; P = 2.2 × 10 –9 ). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.

Original languageEnglish (US)
Pages (from-to)1656-1669
Number of pages14
JournalNature Neuroscience
Volume21
Issue number12
DOIs
StatePublished - Dec 1 2018

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Genome-Wide Association Study
Alcoholism
Psychiatry
Genome
Drinking Behavior
Cannabis
Tobacco Products
Diagnostic and Statistical Manual of Mental Disorders
Alcohol Drinking
Schizophrenia
Depression
Phenotype

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Transancestral GWAS of alcohol dependence reveals common genetic underpinnings with psychiatric disorders. / 23andMe Research Team.

In: Nature Neuroscience, Vol. 21, No. 12, 01.12.2018, p. 1656-1669.

Research output: Contribution to journalArticle

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abstract = "Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest genome-wide association study to date of DSM-IV-diagnosed AD. Genome-wide data on 14,904 individuals with AD and 37,944 controls from 28 case–control and family-based studies were meta-analyzed, stratified by genetic ancestry (European, n = 46,568; African, n = 6,280). Independent, genome-wide significant effects of different ADH1B variants were identified in European (rs1229984; P = 9.8 × 10 –13 ) and African ancestries (rs2066702; P = 2.2 × 10 –9 ). Significant genetic correlations were observed with 17 phenotypes, including schizophrenia, attention deficit–hyperactivity disorder, depression, and use of cigarettes and cannabis. The genetic underpinnings of AD only partially overlap with those for alcohol consumption, underscoring the genetic distinction between pathological and nonpathological drinking behaviors.",
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