| Literature DB >> 29875475 |
Janitza L Montalvo-Ortiz1,2, Hang Zhou1, Ivana D'Andrea3,4,5, Luc Maroteaux3,4,5, Adriana Lori6, Alicia Smith6, Kerry J Ressler7, Yaira Z Nuñez1,2, Lindsay A Farrer8, Hongyu Zhao9,10, Henry R Kranzler11, Joel Gelernter12,13,14,15.
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.Entities:
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Year: 2018 PMID： 29875475 PMCID： PMC6281782 DOI： 10.1038/s41380-018-0077-6
Source DB: PubMed Journal: Mol Psychiatry ISSN： 1359-4184 Impact factor: 15.992