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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.
Schwantes-An, Tae-Hwi; Zhang, Juan; Chen, Li-Shiun; Hartz, Sarah M; Culverhouse, Robert C; Chen, Xiangning; Coon, Hilary; Frank, Josef; Kamens, Helen M; Konte, Bettina; Kovanen, Leena; Latvala, Antti; Legrand, Lisa N; Maher, Brion S; Melroy, Whitney E; Nelson, Elliot C; Reid, Mark W; Robinson, Jason D; Shen, Pei-Hong; Yang, Bao-Zhu; Andrews, Judy A; Aveyard, Paul; Beltcheva, Olga; Brown, Sandra A; Cannon, Dale S; Cichon, Sven; Corley, Robin P; Dahmen, Norbert; Degenhardt, Louisa; Foroud, Tatiana; Gaebel, Wolfgang; Giegling, Ina; Glatt, Stephen J; Grucza, Richard A; Hardin, Jill; Hartmann, Annette M; Heath, Andrew C; Herms, Stefan; Hodgkinson, Colin A; Hoffmann, Per; Hops, Hyman; Huizinga, David; Ising, Marcus; Johnson, Eric O; Johnstone, Elaine; Kaneva, Radka P; Kendler, Kenneth S; Kiefer, Falk; Kranzler, Henry R; Krauter, Ken S.
Afiliación
  • Schwantes-An TH; Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA.
  • Zhang J; 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.
  • Chen LS; Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA.
  • Hartz SM; 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.
  • Culverhouse RC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Chen X; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Coon H; Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Frank J; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
  • Kamens HM; Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA.
  • Konte B; Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
  • Kovanen L; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USA.
  • Latvala A; Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA.
  • Legrand LN; Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, USA.
  • Maher BS; Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
  • Melroy WE; Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland.
  • Nelson EC; Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
  • Reid MW; Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA.
  • Robinson JD; Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
  • Shen PH; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USA.
  • Yang BZ; Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA.
  • Andrews JA; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Aveyard P; Oregon Research Institute, Eugene, OR, 97403, USA.
  • Beltcheva O; Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
  • Brown SA; Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
  • Cannon DS; Department of Psychiatry, Yale University, New Haven, CT, 06516, USA.
  • Cichon S; Oregon Research Institute, Eugene, OR, 97403, USA.
  • Corley RP; Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, United Kingdom.
  • Dahmen N; Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria.
  • Degenhardt L; Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
  • Foroud T; Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA.
  • Gaebel W; Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany.
  • Giegling I; Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
  • Glatt SJ; Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USA.
  • Grucza RA; Ökumenisches Hainich-Klinikum, Mühlhausen/Thüringen, Germany.
  • Hardin J; National Drug and Alcohol Research Centre, University of New South Wales, Randwick, NSW, 2031, Australia.
  • Hartmann AM; School of Population and Global Health, University of Melbourne, Melbourne, 3010, Australia.
  • Heath AC; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
  • Herms S; University of Düsseldorf, 40225, Düsseldorf, Germany.
  • Hodgkinson CA; Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
  • Hoffmann P; Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
  • Hops H; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Huizinga D; Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
  • Ising M; Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
  • Johnson EO; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
  • Johnstone E; Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany.
  • Kaneva RP; Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
  • Kendler KS; Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
  • Kiefer F; Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany.
  • Kranzler HR; Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
  • Krauter KS; Oregon Research Institute, Eugene, OR, 97403, USA.
Behav Genet ; 46(2): 151-69, 2016 Mar.
Article en En | MEDLINE | ID: mdl-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.
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Receptores Opioides mu / Trastornos Relacionados con Sustancias / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Población Blanca / Estudios de Asociación Genética Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Systematic_reviews Idioma: En Revista: Behav Genet Año: 2016 Tipo del documento: Article
Texto completo
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Texto completo: 1 Base de datos: MEDLINE Asunto principal: Receptores Opioides mu / Trastornos Relacionados con Sustancias / Predisposición Genética a la Enfermedad / Polimorfismo de Nucleótido Simple / Población Blanca / Estudios de Asociación Genética Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Systematic_reviews Idioma: En Revista: Behav Genet Año: 2016 Tipo del documento: Article