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Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response.

ABSTRACT: Cannabis use is increasing in the United States, as are its adverse effects. We investigated the genetics of an adverse consequence of cannabis use: cannabis-related aggression (CRA) using a genome-wide association study (GWAS) design. Our GWAS sample included 3269 African Americans (AAs) and 2546 European Americans (EAs). An additional 89 AA subjects from the Grady Trauma Project (GTP) were also examined using a proxy-phenotype replication approach. We identified genome-wide significant risk loci contributing to CRA in AAs at the serotonin receptor 2B receptor gene (HTR2B), and the lead SNP, HTR2B*rs17440378, showed nominal association to aggression in the GTP cohort of cannabis-exposed subjects. A priori evidence linked HTR2B to impulsivity/aggression but not to cannabis response. Human functional data regarding the HTR2B variant further supported our finding. Treating an Htr2b-/- knockout mouse with THC resulted in increased aggressive behavior, whereas wild-type mice following THC administration showed decreased aggression in the resident-intruder paradigm, demonstrating that HTR2B variation moderates the effects of cannabis on aggression. These concordant findings in mice and humans implicate HTR2B as a major locus associated with cannabis-induced aggression.

SUBMITTER: Montalvo-Ortiz JL

PROVIDER: S-EPMC6281782 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response.

Montalvo-Ortiz Janitza L JL Zhou Hang H D'Andrea Ivana I Maroteaux Luc L Lori Adriana A Smith Alicia A Ressler Kerry J KJ Nuñez Yaira Z YZ Farrer Lindsay A LA Zhao Hongyu H Kranzler Henry R HR Gelernter Joel J

Molecular psychiatry 20180606 12

Cannabis use is increasing in the United States, as are its adverse effects. We investigated the genetics of an adverse consequence of cannabis use: cannabis-related aggression (CRA) using a genome-wide association study (GWAS) design. Our GWAS sample included 3269 African Americans (AAs) and 2546 European Americans (EAs). An additional 89 AA subjects from the Grady Trauma Project (GTP) were also examined using a proxy-phenotype replication approach. We identified genome-wide significant risk lo ...[more]

PMID: 29875475

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Dataset Information

Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response.

Publications

Translational studies support a role for serotonin 2B receptor (HTR2B) gene in aggression-related cannabis response.

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