Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
30150663
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.
DATE PUBLISHED
2018 Sep
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2018/01/12
accepted 2018/05/28
pubmed 2018/08/29 06:00
medline 2018/08/29 06:00
entrez 2018/08/29 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Pasman JA Pasman Joëlle A JA Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
Verweij KJH Verweij Karin J H KJH Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands.
Gerring Z Gerring Zachary Z Genetic Epidemiology, Statistical Genetics, and Translational Neurogenomics Laboratories, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Stringer S Stringer Sven S Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Sanchez-Roige S Sanchez-Roige Sandra S Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Treur JL Treur Jorien L JL MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
Abdellaoui A Abdellaoui Abdel A Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands.
Nivard MG Nivard Michel G MG Department of Biological Psychology/Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Baselmans BML Baselmans Bart M L BML Department of Biological Psychology/Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Ong JS Ong Jue-Sheng JS Genetic Epidemiology, Statistical Genetics, and Translational Neurogenomics Laboratories, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Ip HF Ip Hill F HF Department of Biological Psychology/Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
van der Zee MD van der Zee Matthijs D MD Department of Biological Psychology/Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Bartels M Bartels Meike M Department of Biological Psychology/Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Day FR Day Felix R FR MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Fontanillas P Fontanillas Pierre P 23andMe, Inc., Mountain View, CA, USA.
Elson SL Elson Sarah L SL 23andMe, Inc., Mountain View, CA, USA.
23andMe Research Team
de Wit H de Wit Harriet H Department of Psychiatry and Behavioral Neuroscience, University of Chicago, Chicago, IL, USA.
Davis LK Davis Lea K LK Vanderbilt Genetics Institute; Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
MacKillop J MacKillop James J Peter Boris Centre for Addictions Research and Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University/St. Joseph's Healthcare Hamilton, Hamilton, Ontario, Canada.
Substance Use Disorders Working Group of the Psychiatric Genomics Consortium
International Cannabis Consortium
Derringer JL Derringer Jaime L JL Department of Psychology, University of Illinois Urbana-Champaign, Champaign, IL, USA.
Branje SJT Branje Susan J T SJT Department of Youth and Family, Utrecht University, Utrecht, the Netherlands.
Hartman CA Hartman Catharina A CA Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
van Lier PAC van Lier Pol A C PAC Department of Developmental Psychology and EMGO Institute for Health and Care Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Madden PAF Madden Pamela A F PAF Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA.
Mägi R Mägi Reedik R Estonian Genome Center, University of Tartu, Tartu, Estonia.
Meeus W Meeus Wim W Department of Youth and Family, Utrecht University, Utrecht, the Netherlands.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Oldehinkel AJ Oldehinkel A J AJ Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Pausova Z Pausova Zdenka Z Hospital for Sick Children, Toronto, Ontario, Canada.
Ramos-Quiroga JA Ramos-Quiroga Josep A JA Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Paus T Paus Tomas T Departments of Psychology and Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Ribases M Ribases Marta M Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Barcelona, Spain.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine Finland FIMM, HiLIFE Unit, University of Helsinki, Helsinki, Finland.
Boks MPM Boks Marco P M MPM Brain Center Rudolf Magnus, Department of Psychiatry, University Medical Center Utrecht, Utrecht, The Netherlands.
Bell JT Bell Jordana T JT Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Spector TD Spector Tim D TD Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
Gelernter J Gelernter Joel J Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology/Netherlands Twin Register, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Martin NG Martin Nicholas G NG Genetic Epidemiology, Statistical Genetics, and Translational Neurogenomics Laboratories, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
MacGregor S MacGregor Stuart S Genetic Epidemiology, Statistical Genetics, and Translational Neurogenomics Laboratories, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Perry JRB Perry John R B JRB MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK.
Palmer AA Palmer Abraham A AA Institute for Genomic Medicine, University of California San Diego, La Jolla, CA, USA.
Posthuma D Posthuma Danielle D Department of Complex Trait Genetics, Center for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
Munafò MR Munafò Marcus R MR UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol, Bristol, UK.
Gillespie NA Gillespie Nathan A NA Department of Psychiatry, Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Derks EM Derks Eske M EM Genetic Epidemiology, Statistical Genetics, and Translational Neurogenomics Laboratories, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Vink JM Vink Jacqueline M JM Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands. j.vink@bsi.ru.nl.
INVESTIGATORS
JOURNAL
VOLUME: 21
ISSUE: 9
TITLE: Nature neuroscience
ISOABBREVIATION: Nat. Neurosci.
YEAR: 2018
MONTH: Sep
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1726
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Neurosci
COUNTRY: United States
ISSNLINKING: 1097-6256
NLMUNIQUEID: 9809671
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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