Journal article
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
Behavior genetics, Vol.46(2), pp.151-169
03/2016
DOI: 10.1007/s10519-015-9737-3
PMCID: PMC4752855
PMID: 26392368
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.
Details
- Title: Subtitle
- 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
- Creators
- Tae-Hwi Schwantes-An - 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, USAJuan Zhang - 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, ChinaLi-Shiun Chen - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USASarah M Hartz - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USARobert C Culverhouse - Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USAXiangning Chen - Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USAHilary Coon - Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USAJosef Frank - Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, GermanyHelen M Kamens - Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, USABettina Konte - Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), GermanyLeena Kovanen - Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, FinlandAntti Latvala - Department of Public Health, University of Helsinki, Helsinki, 00014, FinlandLisa N Legrand - Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USABrion S Maher - Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USAWhitney E Melroy - Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USAElliot C Nelson - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USAMark W Reid - Oregon Research Institute, Eugene, OR, 97403, USAJason D Robinson - Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAPei-Hong Shen - Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USABao-Zhu Yang - Department of Psychiatry, Yale University, New Haven, CT, 06516, USAJudy A Andrews - Oregon Research Institute, Eugene, OR, 97403, USAPaul Aveyard - Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, United KingdomOlga Beltcheva - Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, BulgariaSandra A Brown - Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USADale S Cannon - Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USASven Cichon - Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, SwitzerlandRobin P Corley - Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USANorbert Dahmen - Ökumenisches Hainich-Klinikum, Mühlhausen/Thüringen, GermanyLouisa Degenhardt - School of Population and Global Health, University of Melbourne, Melbourne, 3010, AustraliaTatiana Foroud - Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USAWolfgang Gaebel - University of Düsseldorf, 40225, Düsseldorf, GermanyIna Giegling - Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), GermanyStephen J Glatt - Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USARichard A Grucza - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USAJill Hardin - Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USAAnnette M Hartmann - Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), GermanyAndrew C Heath - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USAStefan Herms - Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, SwitzerlandColin A Hodgkinson - Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USAPer Hoffmann - Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, SwitzerlandHyman Hops - Oregon Research Institute, Eugene, OR, 97403, USADavid Huizinga - Institute of Behavioral Science, University of Colorado, Boulder, CO, 80309, USAMarcus Ising - Max-Planck-Institute of Psychiatry, 80804, Munich, GermanyEric O Johnson - Behavioral Health Research Division, Research Triangle Institute International, Durham, NC, 27709, USAElaine Johnstone - Department of Oncology, University of Oxford, Oxford, OX3 7DQ, United KingdomRadka P Kaneva - Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, BulgariaKenneth S Kendler - Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USAFalk Kiefer - Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, GermanyHenry R Kranzler - Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USAKen S Krauter - Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80309, USAOrna Levran - Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USASusanne Lucae - Max-Planck-Institute of Psychiatry, 80804, Munich, GermanyMichael T Lynskey - Addictions Department, Institute of Psychiatry, King's College London, London, SE5 8BB, UKWolfgang Maier - University of Bonn, 53113, Bonn, GermanyKarl Mann - Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, GermanyNicholas G Martin - Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, 4029, AustraliaManuel Mattheisen - Aarhus University, Aarhus, 8000, DenmarkGrant W Montgomery - Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, 4029, AustraliaBertram Müller-Myhsok - Max-Planck-Institute of Psychiatry, 80804, Munich, GermanyMichael F Murphy - Childhood Cancer Research Group, University of Oxford, Oxford, OX3 7LG, UKMichael C Neale - Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USAMomchil A Nikolov - Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, BulgariaDenise Nishita - Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USAMarkus M Nöthen - Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, GermanyJohn Nurnberger - Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USATimo Partonen - Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, FinlandMichele L Pergadia - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USAMaureen Reynolds - Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USAMonika Ridinger - Psychiatric Hospital, Konigsfelden, Windisch, SwitzerlandRichard J Rose - Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, USANoora Rouvinen-Lagerström - Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, FinlandNorbert Scherbaum - Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR Hospital Essen, University of Duisburg-Essen, 45147, Essen, GermanyChristine Schmäl - Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, GermanyMichael Soyka - Private Hospital Meiringen, Meiringen, SwitzerlandMichael C Stallings - Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, 80309, USAMichael Steffens - Research Department, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, GermanyJens Treutlein - Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, GermanyMing Tsuang - Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USATamara L Wall - Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USANorbert Wodarz - Department of Psychiatry, University Medical Center Regensburg, University of Regensburg, 8548, Regensburg, GermanyVadim Yuferov - Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USAPeter Zill - University of Munich, Munich, GermanyAndrew W Bergen - Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USAJingchun Chen - Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USAPaul M Cinciripini - Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USAHoward J Edenberg - Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USAMarissa A Ehringer - Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USARobert E Ferrell - Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 15261, USAJoel Gelernter - Department of Neurobiology, Yale University, New Haven, CT, 06516, USADavid Goldman - Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USAJohn K Hewitt - Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, 80309, USAChristian J Hopfer - Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USAWilliam G Iacono - Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USAJaakko Kaprio - Institute for Molecular Medicine FIMM, University of Helsinki, 00014, Helsinki, FinlandMary Jeanne Kreek - Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USAIvo M Kremensky - Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, BulgariaPamela A F Madden - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USAMatt McGue - Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USAMarcus R Munafò - MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, and School of Experimental Psychology, University of Bristol, Bristol, BS8 1TU, UKRobert A Philibert - Department of Psychiatry, University of Iowa, Iowa City, IA, 52242, USAMarcella Rietschel - Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, GermanyAlec Roy - Psychiatry Service, Department of Veteran Affairs, New Jersey VA Health Care System, East Orange, NJ, 07018, USADan Rujescu - Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), GermanySirkku T Saarikoski - Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, FinlandGary E Swan - Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, 94304, USAAlexandre A Todorov - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USAMichael M Vanyukov - Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USARobert B Weiss - Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USALaura J Bierut - Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USANancy L Saccone - Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA. nlims@genetics.wustl.edu
- Resource Type
- Journal article
- Publication Details
- Behavior genetics, Vol.46(2), pp.151-169
- DOI
- 10.1007/s10519-015-9737-3
- PMID
- 26392368
- PMCID
- PMC4752855
- NLM abbreviation
- Behav Genet
- ISSN
- 0001-8244
- eISSN
- 1573-3297
- Publisher
- United States
- Grant note
- P50 DA005130 / NIDA NIH HHS R01 DA012854 / NIDA NIH HHS P01 HL072903 / NHLBI NIH HHS R01 DA12690 / NIDA NIH HHS R01 CA075356 / NCI NIH HHS British Heart Foundation R01 AA013321 / NIAAA NIH HHS R01 DA018823 / NIDA NIH HHS R37 DA005147 / NIDA NIH HHS R56 DA012854 / NIDA NIH HHS K08 DA032680 / NIDA NIH HHS HHSN268200782096C / NHGRI NIH HHS R01 AA11330 / NIAAA NIH HHS K01 DA019498 / NIDA NIH HHS R01 AA13322 / NIAAA NIH HHS R01 AA0011886 / NIAAA NIH HHS R37 AA012502 / NIAAA NIH HHS K05 AA017688 / NIAAA NIH HHS R01 DA026911 / NIDA NIH HHS R01 DA013240 / NIDA NIH HHS P50 AA011998 / NIAAA NIH HHS U01 HG004446 / NHGRI NIH HHS R01 DA18673 / NIDA NIH HHS K01 DA24758 / NIDA NIH HHS P50 DA005605 / NIDA NIH HHS R01 DA036216 / NIDA NIH HHS K08 DA019951 / NIDA NIH HHS 263278 / PHS HHS F31 AA013220 / NIAAA NIH HHS MC_UU_12013/6 / Medical Research Council R01 DA038076 / NIDA NIH HHS R01 AA009203 / NIAAA NIH HHS R01 DA021913 / NIDA NIH HHS R01 DA021905 / NIDA NIH HHS R01 AA11998 / NIAAA NIH HHS R01 AA07728 / NIAAA NIH HHS R01 DA019963 / NIDA NIH HHS R01 CA184781 / NCI NIH HHS DA019498 / NIDA NIH HHS P30 CA016672 / NCI NIH HHS R01 DA005147 / NIDA NIH HHS R01 DA018432 / NIDA NIH HHS K01 DA024758 / NIDA NIH HHS HHSN268200782096C / NHLBI NIH HHS RC2 DA028793 / NIDA NIH HHS R01 DA036583 / NIDA NIH HHS R01 AA017535 / NIAAA NIH HHS R01 AA-09203 / NIAAA NIH HHS U01 HG004422 / NHGRI NIH HHS R21 AA013322 / NIAAA NIH HHS R01 AA13321 / NIAAA NIH HHS R01 AA13220 / NIAAA NIH HHS U10 AA008401 / NIAAA NIH HHS R01 AA17688 / NIAAA NIH HHS U01 HG004438 / NHGRI NIH HHS K07 CA92209 / NCI NIH HHS R01 AA011330 / NIAAA NIH HHS U01 DA024417 / NIDA NIH HHS P01 HL72903 / NHLBI NIH HHS R01 AA012502 / NIAAA NIH HHS R01 FD003706 / FDA HHS R37 AA-12502 / NIAAA NIH HHS R01 DA12849 / NIDA NIH HHS K01 AA019447 / NIAAA NIH HHS K08 DA030398 / NIDA NIH HHS P60 DA011015 / NIDA NIH HHS R01 AA007535 / NIAAA NIH HHS R01 DA013423 / NIDA NIH HHS K24 DA032555 / NIDA NIH HHS P50 DA05130 / NIDA NIH HHS P50 CA070907 / NCI NIH HHS R01 DA012846 / NIDA NIH HHS R01 DA011922 / NIDA NIH HHS R01 DA18432 / NIDA NIH HHS R01 DA012845 / NIDA NIH HHS C53/A6281 / Cancer Research UK R01 DA017305 / NIDA NIH HHS R01 DA018673 / NIDA NIH HHS U01 DA020830 / NIDA NIH HHS R01 DA015789 / NIDA NIH HHS R21 CA081649 / NCI NIH HHS R01 DA11822 / NIDA NIH HHS R01 DA012690 / NIDA NIH HHS K07 CA092209 / NCI NIH HHS R01 DA035804 / NIDA NIH HHS RC2 DA028909 / NIDA NIH HHS 141054 / PHS HHS P60 AA011998 / NIAAA NIH HHS R01 DA12854 / NIDA NIH HHS UL1 TR001108 / NCATS NIH HHS R21 CA81649 / NCI NIH HHS R01 AA013326 / NIAAA NIH HHS K02 AA018755 / NIAAA NIH HHS R01 AA075356 / NIAAA NIH HHS R01 U01 DA024417 / NIDA NIH HHS 1 X01 HG005274-01 / NHGRI NIH HHS R01 AA009367 / NIAAA NIH HHS R01 DA019157 / NIDA NIH HHS R21 DA038241 / NIDA NIH HHS R01 AA013320 / NIAAA NIH HHS R01 AA011886 / NIAAA NIH HHS T32 DA017637 / NIDA NIH HHS R01 AA017889 / NIAAA NIH HHS R01 DA003706 / NIDA NIH HHS R01 DA012849 / NIDA NIH HHS R01 AA007728 / NIAAA NIH HHS R01 MH066140 / NIMH NIH HHS MR/K023195/1 / Medical Research Council P01 CA089392 / NCI NIH HHS
- Language
- English
- Date published
- 03/2016
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984070811402771
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