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
26392368
TITLE
Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts.
ABSTRACT
The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95 % C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.
DATE PUBLISHED
2016 Mar
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2014/12/22
accepted 2015/08/17
aheadofprint 2015/09/21
entrez 2015/09/23 06:00
pubmed 2015/09/24 06:00
medline 2015/09/24 06:00
pmc-release 2017/03/01 00:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Schwantes-An TH Schwantes-An Tae-Hwi TH Genometrics Section, Computational and Statistical Genomics Branch, Division of Intramural Research, National Human Genome Research Institute, US National Institutes of Health (NIH), Baltimore, MD, 21224, USA.
Zhang J Zhang Juan J Key Laboratory of Brain Function and Disease, School of Life Sciences, Chinese Academy of Sciences, University of Science and Technology of China, Hefei, Anhui, 230026, China.
Chen LS Chen Li-Shiun LS Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Hartz SM Hartz Sarah M SM Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Culverhouse RC Culverhouse Robert C RC Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Chen X Chen Xiangning X Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Coon H Coon Hilary H Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA.
Frank J Frank Josef J Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
Kamens HM Kamens Helen M HM Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, USA.
Konte B Konte Bettina B Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
Kovanen L Kovanen Leena L Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland.
Latvala A Latvala Antti A Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
Legrand LN Legrand Lisa N LN Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA.
Maher BS Maher Brion S BS Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
Melroy WE Melroy Whitney E WE Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA.
Nelson EC Nelson Elliot C EC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Reid MW Reid Mark W MW Oregon Research Institute, Eugene, OR, 97403, USA.
Robinson JD Robinson Jason D JD Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Shen PH Shen Pei-Hong PH Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
Yang BZ Yang Bao-Zhu BZ Department of Psychiatry, Yale University, New Haven, CT, 06516, USA.
Andrews JA Andrews Judy A JA Oregon Research Institute, Eugene, OR, 97403, USA.
Aveyard P Aveyard Paul P Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, United Kingdom.
Beltcheva O Beltcheva Olga O Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria.
Brown SA Brown Sandra A SA Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Cannon DS Cannon Dale S DS Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA.
Cichon S Cichon Sven S Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
Corley RP Corley Robin P RP Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USA.
Dahmen N Dahmen Norbert N Ökumenisches Hainich-Klinikum, Mühlhausen/Thüringen, Germany.
Degenhardt L Degenhardt Louisa L School of Population and Global Health, University of Melbourne, Melbourne, 3010, Australia.
Foroud T Foroud Tatiana T Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Gaebel W Gaebel Wolfgang W University of Düsseldorf, 40225, Düsseldorf, Germany.
Giegling I Giegling Ina I Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
Glatt SJ Glatt Stephen J SJ Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
Grucza RA Grucza Richard A RA Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Hardin J Hardin Jill J Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
Hartmann AM Hartmann Annette M AM Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
Heath AC Heath Andrew C AC Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Herms S Herms Stefan S Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
Hodgkinson CA Hodgkinson Colin A CA Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
Hoffmann P Hoffmann Per P Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
Hops H Hops Hyman H Oregon Research Institute, Eugene, OR, 97403, USA.
Huizinga D Huizinga David D Institute of Behavioral Science, University of Colorado, Boulder, CO, 80309, USA.
Ising M Ising Marcus M Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.
Johnson EO Johnson Eric O EO Behavioral Health Research Division, Research Triangle Institute International, Durham, NC, 27709, USA.
Johnstone E Johnstone Elaine E Department of Oncology, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
Kaneva RP Kaneva Radka P RP Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria.
Kendler KS Kendler Kenneth S KS Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Kiefer F Kiefer Falk F Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
Kranzler HR Kranzler Henry R HR Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
Krauter KS Krauter Ken S KS Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA.
Levran O Levran Orna O Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USA.
Lucae S Lucae Susanne S Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.
Lynskey MT Lynskey Michael T MT Addictions Department, Institute of Psychiatry, King's College London, London, SE5 8BB, UK.
Maier W Maier Wolfgang W University of Bonn, 53113, Bonn, Germany.
Mann K Mann Karl K Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
Martin NG Martin Nicholas G NG Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, 4029, Australia.
Mattheisen M Mattheisen Manuel M Aarhus University, Aarhus, 8000, Denmark.
Montgomery GW Montgomery Grant W GW Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, 4029, Australia.
Müller-Myhsok B Müller-Myhsok Bertram B Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.
Murphy MF Murphy Michael F MF Childhood Cancer Research Group, University of Oxford, Oxford, OX3 7LG, UK.
Neale MC Neale Michael C MC Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Nikolov MA Nikolov Momchil A MA Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria.
Nishita D Nishita Denise D Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
Nöthen MM Nöthen Markus M MM Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany.
Nurnberger J Nurnberger John J Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Partonen T Partonen Timo T Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland.
Pergadia ML Pergadia Michele L ML Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Reynolds M Reynolds Maureen M Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Ridinger M Ridinger Monika M Psychiatric Hospital, Konigsfelden, Windisch, Switzerland.
Rose RJ Rose Richard J RJ Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, USA.
Rouvinen-Lagerström N Rouvinen-Lagerström Noora N Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland.
Scherbaum N Scherbaum Norbert N Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
Schmäl C Schmäl Christine C Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
Soyka M Soyka Michael M Private Hospital Meiringen, Meiringen, Switzerland.
Stallings MC Stallings Michael C MC Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, 80309, USA.
Steffens M Steffens Michael M Research Department, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
Treutlein J Treutlein Jens J Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
Tsuang M Tsuang Ming M Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Wall TL Wall Tamara L TL Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
Wodarz N Wodarz Norbert N Department of Psychiatry, University Medical Center Regensburg, University of Regensburg, 8548, Regensburg, Germany.
Yuferov V Yuferov Vadim V Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USA.
Zill P Zill Peter P University of Munich, Munich, Germany.
Bergen AW Bergen Andrew W AW Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
Chen J Chen Jingchun J Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
Cinciripini PM Cinciripini Paul M PM Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Edenberg HJ Edenberg Howard J HJ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Ehringer MA Ehringer Marissa A MA Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA.
Ferrell RE Ferrell Robert E RE Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
Gelernter J Gelernter Joel J Department of Neurobiology, Yale University, New Haven, CT, 06516, USA.
Goldman D Goldman David D Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
Hewitt JK Hewitt John K JK Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, 80309, USA.
Hopfer CJ Hopfer Christian J CJ Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
Iacono WG Iacono William G WG Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA.
Kaprio J Kaprio Jaakko J Institute for Molecular Medicine FIMM, University of Helsinki, 00014, Helsinki, Finland.
Kreek MJ Kreek Mary Jeanne MJ Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USA.
Kremensky IM Kremensky Ivo M IM Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria.
Madden PA Madden Pamela A F PA Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
McGue M McGue Matt M Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA.
Munafò MR Munafò Marcus R MR MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, and School of Experimental Psychology, University of Bristol, Bristol, BS8 1TU, UK.
Philibert RA Philibert Robert A RA Department of Psychiatry, University of Iowa, Iowa City, IA, 52242, USA.
Rietschel M Rietschel Marcella M Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
Roy A Roy Alec A Psychiatry Service, Department of Veteran Affairs, New Jersey VA Health Care System, East Orange, NJ, 07018, USA.
Rujescu D Rujescu Dan D Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
Saarikoski ST Saarikoski Sirkku T ST Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland.
Swan GE Swan Gary E GE Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, 94304, USA.
Todorov AA Todorov Alexandre A AA Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Vanyukov MM Vanyukov Michael M MM Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
Weiss RB Weiss Robert B RB Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.
Bierut LJ Bierut Laura J LJ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
Saccone NL Saccone Nancy L NL Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA. nlims@genetics.wustl.edu.
INVESTIGATORS
JOURNAL
VOLUME: 46
ISSUE: 2
TITLE: Behavior genetics
ISOABBREVIATION: Behav. Genet.
YEAR: 2016
MONTH: Mar
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1573-3297
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Behav Genet
COUNTRY: United States
ISSNLINKING: 0001-8244
NLMUNIQUEID: 0251711
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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U01 DA020830 NIDA NIH HHS United States
U01 DA024417 NIDA NIH HHS United States
U01 HG004422 NHGRI NIH HHS United States
U01 HG004438 NHGRI NIH HHS United States
U10 AA008401 NIAAA NIH HHS United States
GENERAL NOTE
KEYWORDS
KEYWORD
Addiction
Genetic association
OPRM1
Opioid receptor
Single nucleotide polymorphism (SNP)
Substance dependence
MESH HEADINGS
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
OTHER ID's
OTHERID SOURCE
NIHMS724867 [Available on 03/01/17] NLM
PMC4752855 [Available on 03/01/17] NLM