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GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia

Authors :
Pasman, Joëlle A.
Verweij, Karin J.H.
Gerring, Zachary
Stringer, Sven
Sanchez-Roige, Sandra
Treur, Jorien L.
Abdellaoui, Abdel
Nivard, Michel G.
Baselmans, Bart M.L.
Ong, Jue-Sheng
Ip, Hill F.
van der Zee, Matthijs D.
Bartels, Meike
Day, Felix R.
Fontanillas, Pierre
Elson, Sarah L.
de Wit, Harriet
Davis, Lea K.
MacKillop, James
Derringer, Jaime L.
Branje, Susan J.T.
Hartman, Catharina A.
Heath, Andrew C.
van Lier, Pol A.C.
Madden, Pamela A.F.
Mägi, Reedik
Meeus, Wim
Montgomery, Grant W.
Oldehinkel, A.J.
Pausova, Zdenka
Ramos-Quiroga, Josep A.
Paus, Tomas
Ribases, Marta
Kaprio, Jaakko
Boks, Marco P.M.
Bell, Jordana T.
Spector, Tim D.
Gelernter, Joel
Boomsma, Dorret I.
Martin, Nicholas G.
MacGregor, Stuart
Perry, John R.B.
Palmer, Abraham A.
Posthuma, Danielle
Munafò, Marcus R.
Gillespie, Nathan A.
Derks, Eske M.
Vink, Jacqueline M.
Leerstoel Branje
Adolescent development: Characteristics and determinants
Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE)
Source :
Pasman, J A, Verweij, K J H, Gerring, Z, Stringer, S, Sanchez-Roige, S, Treur, J L, Abdellaoui, A, Nivard, M G, Baselmans, B M L, Ong, J-S, Ip, H F, van der Zee, M D, Bartels, M, Day, F R, Fontanillas, P, Elson, S L, de Wit, H, Davis, L K, MacKillop, J, Derringer, J L, Branje, S J T, Hartman, C A, Heath, A C, van Lier, P A C, Madden, P A F, Mägi, R, Meeus, W, Montgomery, G W, Oldehinkel, A J, Pausova, Z, Ramos-Quiroga, J A, Paus, T, Ribases, M, Kaprio, J, Boks, M P M, Bell, J T, Spector, T D, Gelernter, J, Boomsma, D I, Martin, N G, MacGregor, S, Perry, J R B, Palmer, A A, Posthuma, D, Munafò, M R, Gillespie, N A & Derks, E M & Vink, J M 2018, ' GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia ', Nature Neuroscience, vol. 21, no. 9, pp. 1161-1170 . https://doi.org/10.1038/s41593-018-0206-1, Pasman, JA; Verweij, KJH; Gerring, Z; Stringer, S; Sanchez-Roige, S; Treur, JL; et al.(2018). GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia. Nature Neuroscience, 21(9), 1161-1170. doi: 10.1038/s41593-018-0206-1. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/4692767n, Nature neuroscience, 21(9), 1161-1170. NATURE AMERICA INC
Publication Year :
2018

Abstract

© 2018, The Author(s). 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.

Details

Language :
English
ISSN :
10976256
Database :
OpenAIRE
Journal :
Pasman, J A, Verweij, K J H, Gerring, Z, Stringer, S, Sanchez-Roige, S, Treur, J L, Abdellaoui, A, Nivard, M G, Baselmans, B M L, Ong, J-S, Ip, H F, van der Zee, M D, Bartels, M, Day, F R, Fontanillas, P, Elson, S L, de Wit, H, Davis, L K, MacKillop, J, Derringer, J L, Branje, S J T, Hartman, C A, Heath, A C, van Lier, P A C, Madden, P A F, Mägi, R, Meeus, W, Montgomery, G W, Oldehinkel, A J, Pausova, Z, Ramos-Quiroga, J A, Paus, T, Ribases, M, Kaprio, J, Boks, M P M, Bell, J T, Spector, T D, Gelernter, J, Boomsma, D I, Martin, N G, MacGregor, S, Perry, J R B, Palmer, A A, Posthuma, D, Munafò, M R, Gillespie, N A & Derks, E M & Vink, J M 2018, ' GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia ', Nature Neuroscience, vol. 21, no. 9, pp. 1161-1170 . https://doi.org/10.1038/s41593-018-0206-1, Pasman, JA; Verweij, KJH; Gerring, Z; Stringer, S; Sanchez-Roige, S; Treur, JL; et al.(2018). GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia. Nature Neuroscience, 21(9), 1161-1170. doi: 10.1038/s41593-018-0206-1. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/4692767n, Nature neuroscience, 21(9), 1161-1170. NATURE AMERICA INC
Accession number :
edsair.pmid.dedup....f725447858788a1612f1c29739b39ef8