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

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

doi:10.1038/s41593-018-0206-1

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

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

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	1161-1170
Number of pages	10
Journal	Nature Neuroscience
Volume	21
Issue number	9
DOIs	https://doi.org/10.1038/s41593-018-0206-1
Publication status	Published - 1 Sept 2018

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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., 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., ... 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, 21(9), 1161-1170. https://doi.org/10.1038/s41593-018-0206-1

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

abstract = "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.",

author = "Pasman, {Jo{\"e}lle A.} and Verweij, {Karin J. H.} and Zachary Gerring and Sven Stringer and Sandra Sanchez-roige and Treur, {Jorien L.} and Abdel Abdellaoui and Nivard, {Michel G.} and Baselmans, {Bart M. L.} and Jue-sheng Ong and Ip, {Hill F.} and {Van Der Zee}, {Matthijs D.} and Meike Bartels and Day, {Felix R.} and Pierre Fontanillas and Elson, {Sarah L.} and {De Wit}, Harriet and Davis, {Lea K.} and James Mackillop and Derringer, {Jaime L.} and Branje, {Susan J. T.} and Hartman, {Catharina A.} and Heath, {Andrew C.} and {Van Lier}, {Pol A. C.} and Madden, {Pamela A. F.} and Reedik M{\"a}gi and Wim Meeus and Montgomery, {Grant W.} and Oldehinkel, {A. J.} and Zdenka Pausova and Ramos-quiroga, {Josep A.} and Tomas Paus and Marta Ribases and Jaakko Kaprio and Boks, {Marco P. M.} and Bell, {Jordana T.} and Spector, {Tim D.} and Joel Gelernter and Boomsma, {Dorret I.} and Martin, {Nicholas G.} and Stuart Macgregor and Perry, {John R. B.} and Palmer, {Abraham A.} and Danielle Posthuma and Munaf{\`o}, {Marcus R.} and Gillespie, {Nathan A.} and Derks, {Eske M.} and Vink, {Jacqueline M.}",

year = "2018",

month = sep,

day = "1",

doi = "10.1038/s41593-018-0206-1",

language = "English",

volume = "21",

pages = "1161--1170",

journal = "Nature Neuroscience",

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Pasman, JA, Verweij, KJH, Gerring, Z, Stringer, S, Sanchez-roige, S, Treur, JL, Abdellaoui, A, Nivard, MG, Baselmans, BML, Ong, J, Ip, HF, Van Der Zee, MD, Bartels, M, Day, FR, Fontanillas, P, Elson, SL, De Wit, H, Davis, LK, Mackillop, J, Derringer, JL, Branje, SJT, Hartman, CA, Heath, AC, Van Lier, PAC, Madden, PAF, Mägi, R, Meeus, W, Montgomery, GW, Oldehinkel, AJ, Pausova, Z, Ramos-quiroga, JA, Paus, T, Ribases, M, Kaprio, J, Boks, MPM, Bell, JT, Spector, TD, Gelernter, J, Boomsma, DI, Martin, NG, Macgregor, S, Perry, JRB, Palmer, AA, Posthuma, D, Munafò, MR, Gillespie, NA, Derks, EM & Vink, JM 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

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T1 - GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal influence of schizophrenia

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 - 2018/9/1

Y1 - 2018/9/1

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.

U2 - 10.1038/s41593-018-0206-1

DO - 10.1038/s41593-018-0206-1

M3 - Article

SN - 1097-6256

VL - 21

SP - 1161

EP - 1170

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 9

ER -

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

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