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Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium

Translational Psychiatry2016Vol. 6(3), pp. e769–e769

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Sven Stringer, Camelia C. Minică, Karin J. H. Verweij, Hamdi Mbarek, Manon Bernard, Jaime Derringer, Kristel R. van Eijk, Joshua D. Isen, Anu Loukola, Dominique Maciejewski, Evelin Mihailov, Peter J. van der Most, Cristina Sánchez‐Mora, Leonie Roos, Richard Sherva, Raymond K. Walters, Jennifer J. Ware, Abdel Abdellaoui, Tim B. Bigdeli, Susan Branje, Sandra A. Brown, Marcel Bruinenberg, Miguel Casas, Tōnu Esko, Iris Garcia‐Martínez, Scott D. Gordon, Juliette Harris, Catharina A. Hartman, Anjali K. Henders, Andrew C. Heath, Ian B. Hickie, Matthew Hickman, Christian J. Hopfer, Jouke‐Jan Hottenga, Anja C. Huizink, Daniel E. Irons, René S. Kahn, Tellervo Korhonen, Henry R. Kranzler, Kenneth Krauter, P.A.C. van Lier, Gitta H. Lubke, Pamela A. F. Madden, Reedik Mägi, Matt McGue, Sarah E. Medland, Wim Meeus, Michael B. Miller, Grant W. Montgomery, Michel G. Nivard, Ilja M. Nolte, Albertine J. Oldehinkel, Zdenka Pausová, Beenish Qaiser, Lydia Quaye, Josep Antoni Ramos‐Quiroga, Vanesa Richarte, Richard J. Rose, Jisu Shin, Michael C. Stallings, Alexander Stiby, Tamara L. Wall, Margaret J. Wright, Hans M. Koot, Tomáš Paus, John K. Hewitt, Marta Ribasès, Jaakko Kaprio, Marco P. Boks, Harold Snieder, Tim D. Spector, Marcus R. Munafò, Andres Metspalu, Joel Gelernter, Dorret I. Boomsma, William G. Iacono, Nicholas G. Martin, Nathan A. Gillespie, Eske M. Derks, Jacqueline M. Vink

Abstract

Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N=32 330) and four replication samples (N=5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P<0.001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (rg=0.83; P=1.85 × 10(-8)) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.

Citations Over TimeTop 1% of 2016 papers

Abstract

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