Genome-wide association study of lifetime cannabis use based on a large meta-analytic sample of 32 330 subjects from the International Cannabis Consortium
Stringer, Sven (Department of Psychiatry, Academic Medical Centre Amsterdam)
Minica, C. C. (Department of Biological Psychology/Netherlands Twin Register, VU University)
Verweij, Karin (Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University)
Mbarek, Hamdi (Department of Biological Psychology/Netherlands Twin Register, VU University)
Bernard, Manon (The Hospital for Sick Children Research Institute (Toronto, Canadà))
Derringer, Jaime (Department of Psychology, University of Illinois Urbana-Champaign)
van Eijk, Kristel R. (Department of Human Neurogenetics, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Isen, Joshua (Department of Psychology, University of Minnesota)
Loukola, Anu-Maria (Department of Public Health, Hjelt Institute, University of Helsinki)
Maciejewski, Dominique F. (Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University)
Mihailov, Evelin (Estonian Genome Center, University of Tartu)
van der Most, Peter J. (Department of Epidemiology, University Medical Center Groningen, University of Groningen)
Sánchez-Mora, Cristina (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Roos, Leonie (King's College London)
Sherva, Richard (Biomedical Genetics Department, Boston University School of Medicine)
Walters, Raymond K. (Department of Medicine, Harvard Medical School)
Ware, Jennifer J. (MRC Integrative Epidemiology Unit (IEU), University of Bristol)
Abdellaoui, Abdel (Department of Biological Psychology/Netherlands Twin Register, VU University)
Bigdeli, Tim B. (Department of Psychiatry, Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University)
Branje, Susan (Research Centre Adolescent Development, Utrecht University)
Brown, S. A. (Department of Psychology and Psychiatry, University of California San Diego)
Bruinenberg, M. (The LifeLines Cohort Study, University of Groningen)
Casas, M. (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Esko, T. (Estonian Genome Center, University of Tartu)
García-Martinez, Iris (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Gordon, Scott D. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Harris, J. M. (King's College London)
Hartman, Catharina A (Department of Psychiatry, University Medical Center Groningen, University of Groningen)
Henders, Anjali K (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Heath, A. C. (Department of Psychiatry, Washington University School of Medicine)
Hickie, Ian B. (Brain and Mind Research Institute, University of Sydney)
Hickman, M. (School of Social and Community Medicine, University of Bristol)
Hopfer, C. J. (Department of Psychiatry, University of Colorado Denver)
Hottenga, J. J. (Department of Biological Psychology/Netherlands Twin Register, VU University)
Huizink, A. C. (Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University)
Irons, D. E. (Department of Psychology, University of Minnesota)
Kahn, R. S. (Department of Human Neurogenetics, Brain Center Rudolf Magnus, University Medical Center Utrecht)
Korhonen, T. (Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare)
Kranzler, H. R. (Department of Psychiatry, University of Pennsylvania Perelman School of Medicine)
Krauter, K. (Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder)
van Lier, P. A. C. (Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University)
Lubke, G. H. (Department of Psychology, University of Notre Dame)
Madden, P. A. F. (Department of Psychiatry, Washington University School of Medicine)
Mägi, Reedik (Estonian Genome Center, University of Tartu)
McGue, M. K. (Department of Psychology, University of Minnesota)
Medland, S. E. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Meeus, W. H. J. (Developmental Psychology, Tilburg University)
Miller, M. B. (Department of Psychology, University of Minnesota)
Montgomery, G. W. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Nivard, M. G. (Department of Biological Psychology/Netherlands Twin Register, VU University)
Nolte, Ilja Maria (University Medical Center Groningen, University of Groningen)
Oldehinkel, Albertine J. (Interdisciplinary Center for Pathology and Emotion Regulation, University Medical Center Groningen, University of Groningen)
Pausova, Zdenka (University of Toronto)
Qaiser, Beenish (Hjelt Institute, University of Helsinki)
Quaye, Lydia (King's College London)
Ramos-Quiroga, Josep Antoni (Universitat Autònoma de Barcelona. Departament de Psiquiatria i de Medicina Legal)
Richarte, Vanesa (Hospital Universitari Vall d'Hebron)
Rose, Richard J. (Indiana University Bloomington)
Shin, Jean (The Hospital for Sick Children Research Institute (Toronto, Canàda))
Stallings, Michael C. (Institute for Behavioral Genetics, University of Colorado Boulder)
Stiby, Alexander I (School of Social and Community Medicine, University of Bristol)
Wall, Tamara L. (University of California San Diego)
Wright, Margaret J (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Koot, Hans (Department of Developmental Psychology and EMGO Institute for Health and Care Research, VU University)
Paus, Tomáš (Center for the Developing Brain, Child Mind Institute New York)
Hewitt, John (University of Colorado Boulder. Department of Psychology and Neuroscience)
Ribasés Haro, Marta (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Kaprio, Jaakko (Institute for Molecular Medicine Finland, University of Helsinki)
Boks, Marco P. (Brain Center Rudolf Magnus, University Medical Center Utrecht)
Snieder, Harold (University Medical Center Groningen)
Spector, Tim David (King's College London)
Munafo, Marcus (UK Centre for Tobacco and Alcohol Studies and School of Experimental Psychology, University of Bristol)
Metspalu, Andres (University of Tartu. Estonian Genome Center (Estònia))
Gelernter, Joel E. (Yale University School of Medicine and VA CT)
Boomsma, Dorret I. (Neuroscience Campus Amsterdam)
Iacono, William G. (University of Minnesota)
Martin, Nicholas G. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Gillespie, Nathan A. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Derks, Eske M. (Academic Medical Centre)
Vink, Jacqueline M. (Behavioural Science Institute, Radboud University)
Universitat Autònoma de Barcelona

Data:	2016
Resum:	Cannabis is the most widely produced and consumed illicit psychoactive substance worldwide. Occasional cannabis use can progress to frequent use, abuse and dependence with all known adverse physical, psychological and social consequences. Individual differences in cannabis initiation are heritable (40-48%). The International Cannabis Consortium was established with the aim to identify genetic risk variants of cannabis use. We conducted a meta-analysis of genome-wide association data of 13 cohorts (N =32 330) and four replication samples (N =5627). In addition, we performed a gene-based test of association, estimated single-nucleotide polymorphism (SNP)-based heritability and explored the genetic correlation between lifetime cannabis use and cigarette use using LD score regression. No individual SNPs reached genome-wide significance. Nonetheless, gene-based tests identified four genes significantly associated with lifetime cannabis use: NCAM1, CADM2, SCOC and KCNT2. Previous studies reported associations of NCAM1 with cigarette smoking and other substance use, and those of CADM2 with body mass index, processing speed and autism disorders, which are phenotypes previously reported to be associated with cannabis use. Furthermore, we showed that, combined across the genome, all common SNPs explained 13-20% (P <0. 001) of the liability of lifetime cannabis use. Finally, there was a strong genetic correlation (r =0. 83; P =1. 85 × 10 −8) between lifetime cannabis use and lifetime cigarette smoking implying that the SNP effect sizes of the two traits are highly correlated. This is the largest meta-analysis of cannabis GWA studies to date, revealing important new insights into the genetic pathways of lifetime cannabis use. Future functional studies should explore the impact of the identified genes on the biological mechanisms of cannabis use.
Ajuts:	European Commission 284167
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Translational psychiatry, Vol. 6 (03 2016) , p. e769, ISSN 2158-3188

DOI: 10.1038/tp.2016.36
PMID: 27023175

9 p, 1.1 MB

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