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 23andMe Research Team
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
Y1 - 2018
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052700617&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30150663
U2 - https://doi.org/10.1038/s41593-018-0206-1
DO - https://doi.org/10.1038/s41593-018-0206-1
M3 - Article
C2 - 30150663
SN - 1097-6256
VL - 21
SP - 1161
EP - 1170
JO - Nature neuroscience
JF - Nature neuroscience
IS - 9
ER -