TY - JOUR
T1 - GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia
AU - the 23 and Me Research Team
AU - The Substance Use Disorders Working Group of the Psychiatric Genomics Consortium
AU - International Cannabis Consortium
AU - Pasman, Joëlle A.
AU - Verweij, Karin J.H.
AU - Gerring, Zachary
AU - Stringer, Sven
AU - Sanchez-Roige, Sandra
AU - Treur, Jorien L.
AU - Abdellaoui, Abdel
AU - Nivard, Michel G.
AU - Baselmans, Bart M.L.
AU - Ong, Jue Sheng
AU - Ip, Hill F.
AU - van der Zee, Matthijs D.
AU - Bartels, Meike
AU - Day, Felix R.
AU - Fontanillas, Pierre
AU - Elson, Sarah L.
AU - de Wit, Harriet
AU - Davis, Lea K.
AU - MacKillop, James
AU - Derringer, Jaime L.
AU - Branje, Susan J.T.
AU - Hartman, Catharina A.
AU - Heath, Andrew C.
AU - van Lier, Pol A.C.
AU - Madden, Pamela A.F.
AU - Mägi, Reedik
AU - Meeus, Wim
AU - Montgomery, Grant W.
AU - Oldehinkel, A. J.
AU - Pausova, Zdenka
AU - Ramos-Quiroga, Josep A.
AU - Paus, Tomas
AU - Ribases, Marta
AU - Kaprio, Jaakko
AU - Boks, Marco P.M.
AU - Bell, Jordana T.
AU - Spector, Tim D.
AU - Gelernter, Joel
AU - Boomsma, Dorret I.
AU - Martin, Nicholas G.
AU - MacGregor, Stuart
AU - Perry, John R.B.
AU - Palmer, Abraham A.
AU - Posthuma, Danielle
AU - Munafò, Marcus R.
AU - Gillespie, Nathan A.
AU - Derks, Eske M.
AU - Vink, Jacqueline M.
PY - 2018/9
Y1 - 2018/9
N2 - Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study for lifetime cannabis use to date (N=184,765), we identified 8 genome-wide significant independent single nucleotide polymorphisms in 6 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 non-users. 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 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 gives new insights about the etiology of cannabis use and its relation with mental health.
AB - Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study for lifetime cannabis use to date (N=184,765), we identified 8 genome-wide significant independent single nucleotide polymorphisms in 6 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 non-users. 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 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 gives new insights about the etiology of cannabis use and its relation with mental health.
UR - http://www.scopus.com/inward/record.url?scp=85052700617&partnerID=8YFLogxK
U2 - 10.1038/s41593-018-0206-1
DO - 10.1038/s41593-018-0206-1
M3 - Article (Academic Journal)
C2 - 30150663
AN - SCOPUS:85052700617
SN - 1097-6256
VL - 21
SP - 1161
EP - 1170
JO - Nature Neuroscience
JF - Nature Neuroscience
IS - 9
ER -
