Authors
Joëlle A Pasman, Karin JH Verweij, Zachary Gerring, Sven Stringer, Sandra Sanchez-Roige, Jorien L Treur, Abdel Abdellaoui, Michel G Nivard, Bart ML Baselmans, Jue-Sheng Ong, Hill F Ip, Matthijs D Van Der Zee, Meike Bartels, Felix R Day, Pierre Fontanillas, Sarah L Elson, 23andMe Research Team, Harriet de Wit, Lea K Davis, James MacKillop, Substance Use Disorders Working Group of the Psychiatric Genomics Consortium, International Cannabis Consortium, Jaime L Derringer, Susan JT Branje, Catharina A Hartman, Andrew C Heath, Pol AC van Lier, Pamela AF Madden, Reedik Mägi, Wim Meeus, Grant W Montgomery, AJ Oldehinkel, Zdenka Pausova, Josep A Ramos-Quiroga, Tomas Paus, Marta Ribases, Jaakko Kaprio, Marco PM Boks, Jordana T Bell, Tim D Spector, Joel Gelernter, Dorret I Boomsma, Nicholas G Martin, Stuart MacGregor, John RB Perry, Abraham A Palmer, Danielle Posthuma, Marcus R Munafò, Nathan A Gillespie, Eske M Derks, Jacqueline M Vink
Publication date
2018/9
Journal
Nature neuroscience
Volume
21
Issue
9
Pages
1161-1170
Publisher
Nature Publishing Group US
Description
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 …
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