Genetic Epidemiology, Psychiatric Genetics, Asthma 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
30003630
TITLE
Genome-wide association meta-analysis of age at first cannabis use.
ABSTRACT
BACKGROUND AND AIMS NlmCategory: OBJECTIVE
Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.
METHODS NlmCategory: METHODS
A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.
RESULTS NlmCategory: RESULTS
 > 0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.
CONCLUSION NlmCategory: CONCLUSIONS
Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders.
2018 Society for the Study of Addiction.
DATE PUBLISHED
2018 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2017/11/03
revised 2018/01/26
accepted 2018/06/11
pubmed 2018/07/14 06:00
medline 2018/07/14 06:00
entrez 2018/07/14 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Minică CC Minică Camelia C CC Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam, the Netherlands.
Verweij KJH Verweij Karin J H KJH Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam, the Netherlands.
van der Most PJ van der Most Peter J PJ Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Mbarek H Mbarek Hamdi H Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam, the Netherlands.
Bernard M Bernard Manon M Hospital for Sick Children Research Institute, Toronto, Canada.
van Eijk KR van Eijk Kristel R KR Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Lind PA Lind Penelope A PA Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Liu MZ Liu Meng Zhen MZ Institute for Behavioral Genetics, Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Maciejewski DF Maciejewski Dominique F DF GGZ inGeest and Department of Psychiatry, Amsterdam Public Health Research Institute, VU University Medical Center, Amsterdam, the Netherlands.
Palviainen T Palviainen Teemu T Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Sánchez-Mora C Sánchez-Mora Cristina C Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
Sherva R Sherva Richard R Biomedical Genetics Department, Boston University School of Medicine, Boston, MA, USA.
Taylor M Taylor Michelle M School of Social and Community Medicine, University of Bristol, Bristol, UK.
Walters RK Walters Raymond K RK Department of Medicine, Harvard Medical School, Boston, MA, USA.
Abdellaoui A Abdellaoui Abdel A Amsterdam UMC, University of Amsterdam, Department of Psychiatry, Amsterdam, the Netherlands.
Bigdeli TB Bigdeli Timothy B TB Department of Psychiatry, Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Branje SJT Branje Susan J T SJT Research Centre Adolescent Development, Utrecht University, Utrecht, the Netherlands.
Brown SA Brown Sandra A SA Department of Psychology and Psychiatry, University of California San Diego, La Jolla, CA, USA.
Casas M Casas Miguel M Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Corley RP Corley Robin P RP Institute for Behavioral Genetics, Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Davey-Smith G Davey-Smith George G School of Social and Community Medicine, University of Bristol, Bristol, UK.
Davies GE Davies Gareth E GE Avera Institute for Human Genetics, Sioux Falls, SD, USA.
Ehli EA Ehli Erik A EA Avera Institute for Human Genetics, Sioux Falls, SD, USA.
Farrer L Farrer Lindsay L Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.
Fedko IO Fedko Iryna O IO Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam, the Netherlands.
Garcia-Martínez I Garcia-Martínez Iris I Department of Psychiatry, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Gordon SD Gordon Scott D SD Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Hartman CA Hartman Catharina A CA Department of Psychiatry, 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.
Hickie IB Hickie Ian B IB Brain and Mind Research Institute, University of Sydney, Sydney, NSW, Australia.
Hickman M Hickman Matthew M School of Social and Community Medicine, University of Bristol, Bristol, UK.
Hopfer CJ Hopfer Christian J CJ Department of Psychiatry, University of Colorado Denver, Aurora, CO, USA.
Hottenga JJ Hottenga Jouke Jan JJ Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam, the Netherlands.
Kahn RS Kahn René S RS Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Kaprio J Kaprio Jaakko J Department of Public Health, University of Helsinki, Helsinki, Finland.
Korhonen T Korhonen Tellervo T University of Eastern Finland, Institute of Public Health and Clinical Nutrition, Kuopio, Finland.
Kranzler HR Kranzler Henry R HR Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Krauter K Krauter Ken K Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, CO, USA.
van Lier PAC van Lier Pol A C PAC Department of Psychology, Education and Child Studies, Erasmus University Rotterdam, Rotterdam, the Netherlands.
Madden PAF Madden Pamela A F PAF Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA.
Medland SE Medland Sarah E SE Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Neale MC Neale Michael C MC Department of Psychiatry and School of Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Meeus WHJ Meeus Wim H J WHJ Developmental Psychology, Tilburg University, Tilburg, the Netherlands.
Montgomery GW Montgomery Grant W GW Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia.
Nolte IM Nolte Ilja M IM Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Oldehinkel AJ Oldehinkel Albertine J AJ Department of Psychiatry, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Pausova Z Pausova Zdenka Z Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada.
Ramos-Quiroga JA Ramos-Quiroga Josep A JA Department of Psychiatry and Legal Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
Richarte V Richarte Vanesa V Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
Rose RJ Rose Richard J RJ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
Shin J Shin Jean J Hospital for Sick Children Research Institute, Toronto, Canada.
Stallings MC Stallings Michael C MC Institute for Behavioral Genetics, Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Wall TL Wall Tamara L TL Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.
Ware JJ Ware Jennifer J JJ School of Social and Community Medicine, University of Bristol, Bristol, UK.
Wright MJ Wright Margaret J MJ Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia.
Zhao H Zhao Hongyu H Department of Biostatistics, Yale School of Public Health and VA CT, New Haven, CT, USA.
Koot HM Koot Hans M HM Department of Clinical Developmental Psychology, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
Paus T Paus Tomas T Center for the Developing Brain, Child Mind Institute, New York, NY, USA.
Hewitt JK Hewitt John K JK Institute for Behavioral Genetics, Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, CO, USA.
Ribasés M Ribasés Marta M Biomedical Network Research Centre on Mental Health (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
Loukola A Loukola Anu A Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
Boks MP Boks Marco P MP Department of Psychiatry, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands.
Snieder H Snieder Harold H Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
Munafò MR Munafò Marcus R MR UK Centre for Tobacco and Alcohol Studies, School of Experimental Psychology, University of Bristol, Bristol, UK.
Gelernter J Gelernter Joel J Psychiatry, Genetics, and Neuroscience, Yale University School of Medicine and VA CT, West Haven, CT, USA.
Boomsma DI Boomsma Dorret I DI Department of Biological Psychology/Netherlands Twin Register, VU University, Amsterdam, the Netherlands.
Martin NG Martin Nicholas G NG Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Gillespie NA Gillespie Nathan A NA Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Vink JM Vink Jacqueline M JM Behavioral Science Institute, Radboud University, Nijmegen, the Netherlands.
Derks EM Derks Eske M EM Translational Neurogenomics group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
INVESTIGATORS
JOURNAL
VOLUME: 113
ISSUE: 11
TITLE: Addiction (Abingdon, England)
ISOABBREVIATION: Addiction
YEAR: 2018
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1360-0443
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Addiction
COUNTRY: England
ISSNLINKING: 0965-2140
NLMUNIQUEID: 9304118
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
GRANTS
GRANTID AGENCY COUNTRY
NARSAD Young Investigator Grant Brain & Behavior Research Foundation
ERC-284167 European Research Council International
Foundation Volksbond Rotterdam
NSF BCS-1229450 NIH HHS United States
NIH U01 MH094432 NIH HHS United States
NWO 480-05-003 NWO
DA-018673 NIDA NIH HHS United States
R00DA023549 US National Institutes of Health, National Institute on Drug Abuse
GENERAL NOTE
KEYWORDS
KEYWORD
ATP2C2
Age at first use
cannabis initiation
genome-wide association
heritability
substance use
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's