“GWAS of Lifetime Cannabis Use Reveals New Risk Loci, Genetic Overlap With Psychiatric Traits, and a Causal Influence of Schizophrenia”, Joëlle A. Pasman, Karin J. H. Verweij, Zachary Gerring, Sven Stringer, Sandra Sanchez-Roige, Jorien L. Treur, Abdel Abdellaoui, Michel G. Nivard, Bart M. L. Baselmans, Jue-Sheng Ong, Hill F. Ip, Matthijs D. van der Zee, Meike Bartels, Felix R. Day, Pierre Fontanillas, Sarah L. Elson, Harriet de Wit, Lea K. Davis, James MacKillop, Jaime L. Derringer, Susan J. T. Branje, Catharina A. Hartman, Andrew C. Heath, Pol A. C. van Lier, Pamela A. F. Madden, Reedik Mägi, Wim Meeus, Grant W. Montgomery, A. J. Oldehinkel, Zdenka Pausova, Josep A. Ramos-Quiroga, Tomas Paus, Marta Ribases, Jaakko Kaprio, Marco P. M. Boks, Jordana T. Bell, Tim D. Spector, Joel Gelernter, Dorret I. Boomsma, Nicholas G. Martin, Stuart MacGregor, John R. B. Perry, Abraham Palmer, Danielle Posthuma, Marcus R. Munafò, Nathan A. Gillespie, Eske M. Derks, Jacqueline M. Vink2018 (, , ; similar)⁠:

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 8 genome-wide statistically-significant independent single-nucleotide polymorphisms in 6 regions. All measured genetic variants combined explained 11% of the variance.

Gene-based tests revealed 35 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.

Genetic correlations were found with 14⁄25 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.