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

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions....

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Published in:Nature neuroscience Vol. 21; no. 9; p. 1161
Main Authors: Pasman, Joëlle A, Verweij, Karin J H, Gerring, Zachary, Stringer, Sven, Sanchez-Roige, Sandra, Treur, Jorien L, Abdellaoui, Abdel, Nivard, Michel G, Baselmans, Bart M L, Ong, Jue-Sheng, Ip, Hill F, van der Zee, Matthijs D, Bartels, Meike, Day, Felix R, Fontanillas, Pierre, Elson, Sarah L, de Wit, Harriet, Davis, Lea K, MacKillop, James, Derringer, Jaime L, Branje, Susan J T, Hartman, Catharina A, Heath, Andrew C, van Lier, Pol A C, Madden, Pamela A F, Mägi, Reedik, Meeus, Wim, Montgomery, Grant W, Oldehinkel, A J, Pausova, Zdenka, Ramos-Quiroga, Josep A, Paus, Tomas, Ribases, Marta, Kaprio, Jaakko, Boks, Marco P M, Bell, Jordana T, Spector, Tim D, Gelernter, Joel, Boomsma, Dorret I, Martin, Nicholas G, MacGregor, Stuart, Perry, John R B, Palmer, Abraham A, Posthuma, Danielle, Munafò, Marcus R, Gillespie, Nathan A, Derks, Eske M, Vink, Jacqueline M
Format: Journal Article
Language:English
Published: United States 01.09.2018
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Cell Adhesion Molecules - genetics
Databases, Genetic
Female
Gene Expression Regulation - genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Marijuana Abuse - genetics
Marijuana Abuse - psychology
Mendelian Randomization Analysis
Mental Health
Middle Aged
Polymorphism, Single Nucleotide
Risk-Taking
Schizophrenia - chemically induced
Schizophrenia - genetics
Young Adult
ISSN:1546-1726, 1546-1726
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Summary:Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six 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 nonusers. 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-related 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 provides new insights into the etiology of cannabis use and its relation with mental health.
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ISSN:1546-1726
1546-1726
DOI:10.1038/s41593-018-0206-1