GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia

the 23 and Me Research Team, The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Joëlle A. Pasman, Karin J.H. Verweij, Jacqueline M. Vink*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

101 Citations (Scopus)
442 Downloads (Pure)

Abstract

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study for lifetime cannabis use to date (N=184,765), we identified 8 genome-wide significant independent single nucleotide polymorphisms in 6 regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus non-users. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health traits, including smoking, alcohol use, schizophrenia, and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study gives new insights about the etiology of cannabis use and its relation with mental health.
Original languageEnglish
Pages (from-to)1161-1170
Number of pages10
JournalNature Neuroscience
Volume21
Issue number9
Early online date27 Aug 2018
DOIs
Publication statusPublished - Sep 2018

Structured keywords

  • Brain and Behaviour
  • Tobacco and Alcohol
  • Physical and Mental Health

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