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

by Oldehinkel, A J , Boomsma, Dorret I , Elson, Sarah L , Meeus, Wim , Vink, Jacqueline M , Derks, Eske M , Abdellaoui, Abdel , Boks, Marco P M , Posthuma, Danielle , Baselmans, Bart M L , Madden, Pamela A F , Munafò, Marcus R , Heath, Andrew C , Palmer, Abraham A , Stringer, Sven , Pasman, Joëlle A , Paus, Tomas , Montgomery, Grant W , Treur, Jorien L , Jue-Sheng Ong , de Wit, Harriet , Branje, Susan J T , Martin, Nicholas G , Gillespie, Nathan A , Ribases, Marta , Bartels, Meike , Derringer, Jaime L , Davis, Lea K , Nivard, Michel G , Ramos-Quiroga, Josep A , Pol A C van Lier , Pausova, Zdenka , Matthijs D van der Zee , Hartman, Catharina A , Ip, Hill F , Kaprio, Jaakko , Spector, Tim D , Gerring, Zachary , Gelernter, Joel , MacGregor, Stuart , Sanchez-Roige, Sandra , Day, Felix R , Reedik Mägi , Perry, John R B , Fontanillas, Pierre , Bell, Jordana T , MacKillop, James , Verweij, Karin J H

in Alcoholic beverages / Cannabis / Drug abuse / Drug use / Etiology / Gene expression / Genes / Genetic diversity / Genetic variance / Genome-wide association studies / Genomes / Marijuana / Mental disorders / Mental health / Risk analysis / Risk taking / Schizophrenia / Single-nucleotide polymorphism / Smoking / Substance use

2018

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

2018

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

2018

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Journal Article

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

Oldehinkel, A J,

Boomsma, Dorret I,

Elson, Sarah L,

Meeus, Wim,

Vink, Jacqueline M,

Derks, Eske M,

Abdellaoui, Abdel,

Boks, Marco P M,

Posthuma, Danielle,

Baselmans, Bart M L,

Madden, Pamela A F,

Munafò, Marcus R,

Heath, Andrew C,

Palmer, Abraham A,

Stringer, Sven,

Pasman, Joëlle A,

Paus, Tomas,

Montgomery, Grant W,

Treur, Jorien L,

Jue-Sheng Ong,

de Wit, Harriet,

Branje, Susan J T,

Martin, Nicholas G,

Gillespie, Nathan A,

Ribases, Marta,

Bartels, Meike,

Derringer, Jaime L,

Davis, Lea K,

Nivard, Michel G,

Ramos-Quiroga, Josep A,

Pol A C van Lier,

Pausova, Zdenka,

Matthijs D van der Zee,

Hartman, Catharina A,

Ip, Hill F,

Kaprio, Jaakko,

Spector, Tim D,

Gerring, Zachary,

Gelernter, Joel,

MacGregor, Stuart,

Sanchez-Roige, Sandra,

Day, Felix R,

Reedik Mägi,

Perry, John R B,

Fontanillas, Pierre,

Bell, Jordana T,

MacKillop, James,

Verweij, Karin J H

2018

Overview

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.

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Publisher

Nature Publishing Group

Subject

/ Genes