ArticleJournal of studies on alcohol and drugs2019
Effects of Common and Rare Chromosome 4 GABAergic Gene Variation on Alcohol Use and Antisocial Behavior.
Article in Journal of studies on alcohol and drugs, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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5 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveEpidemiological estimates suggest that nearly half of individuals diagnosed with alcohol use disorder will be diagnosed with another mental health disorder, with strong associations involving other externalizing disorders. Molecular genetic studies investigating the relation between alcohol use disorder and externalizing behaviors (e.g., antisocial behavior) have focused on a cluster of chromosome 4 γ-aminobutyric acid (GABA) receptor genes (GABRG1-A2-A4-B1) but have generated varying results.
methodThe current study examined associations between common and rare variation in this region with alcohol use disorder and antisocial behavior using genetic sequencing data. Specifically, the University of California at San Francisco Family Alcoholism Sample (n = 1,610; 62% female) was used to conduct common and rare variant association tests in the GABRG1-A2-A4-B1 cluster with DSM-5 alcohol use disorder symptom counts, antisocial behavior, and a product term representing their interaction.
resultsGene-based analyses of rare variation resulted in a significant association between rare GABRA2 variation and the interaction term. Single-variant analysis yielded only nominally significant associations. The strongest association for alcohol use disorder (rs3756007) was located in GABRA2, the strongest association for antisocial behavior (rs11941860) was located in GABRG1, and the interaction term yielded top associations in GABRA2 (rs2119183) and the intergenic region between GABRA2 and GABRG1 (rs536599). Common and rare variant associations for the interaction remained similar when covarying for the effects of the other type of variation, suggesting that the significant rare variant signal is independent of common variant contributions.
conclusionsThe present study suggests that both rare and common variant associations in GABRA2 confer risk for alcohol use disorder and antisocial behaviors, indicating a potential liability toward externalizing behavior more broadly.
Indexed as
Identifiers
31790348PMC6900988W2991815054What OpenQuestion holds
Registered trials
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