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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Veröffentlicht in:	Nature neuroscience Jg. 21; H. 9; S. 1161
Hauptverfasser:	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
Sprache:	Englisch
Veröffentlicht:	United States 01.09.2018
Schlagworte:	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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Zusammenfassung:	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.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1546-1726 1546-1726
DOI:	10.1038/s41593-018-0206-1