Meta-Analysis

. 2016 Mar;46(2):151-69.

doi: 10.1007/s10519-015-9737-3. Epub 2015 Sep 21.

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

Tae-Hwi Schwantes-An^{1

2}, Juan Zhang^{1

3}, Li-Shiun Chen⁴, Sarah M Hartz⁴, Robert C Culverhouse⁵, Xiangning Chen⁶, Hilary Coon⁷, Josef Frank⁸, Helen M Kamens^{9

10

11}, Bettina Konte¹², Leena Kovanen¹³, Antti Latvala¹⁴, Lisa N Legrand¹⁵, Brion S Maher¹⁶, Whitney E Melroy^{9

10}, Elliot C Nelson⁴, Mark W Reid¹⁷, Jason D Robinson¹⁸, Pei-Hong Shen¹⁹, Bao-Zhu Yang²⁰, Judy A Andrews¹⁷, Paul Aveyard²¹, Olga Beltcheva²², Sandra A Brown²³, Dale S Cannon⁷, Sven Cichon^{24

25}, Robin P Corley⁹, Norbert Dahmen²⁶, Louisa Degenhardt^{27

28}, Tatiana Foroud²⁹, Wolfgang Gaebel³⁰, Ina Giegling¹², Stephen J Glatt³¹, Richard A Grucza⁴, Jill Hardin³², Annette M Hartmann¹², Andrew C Heath⁴, Stefan Herms^{24

25}, Colin A Hodgkinson¹⁹, Per Hoffmann^{24

25}, Hyman Hops¹⁷, David Huizinga³³, Marcus Ising³⁴, Eric O Johnson³⁵, Elaine Johnstone³⁶, Radka P Kaneva²², Kenneth S Kendler⁶, Falk Kiefer³⁷, Henry R Kranzler³⁸, Ken S Krauter^{9

39}, Orna Levran⁴⁰, Susanne Lucae³⁴, Michael T Lynskey⁴¹, Wolfgang Maier⁴², Karl Mann⁴³, Nicholas G Martin⁴⁴, Manuel Mattheisen^{24

45

46}, Grant W Montgomery⁴⁴, Bertram Müller-Myhsok³⁴, Michael F Murphy⁴⁷, Michael C Neale⁶, Momchil A Nikolov^{4

22}, Denise Nishita³², Markus M Nöthen²⁴, John Nurnberger⁴⁸, Timo Partonen¹³, Michele L Pergadia⁴, Maureen Reynolds⁴⁹, Monika Ridinger^{50

51}, Richard J Rose⁵², Noora Rouvinen-Lagerström¹³, Norbert Scherbaum⁵³, Christine Schmäl⁴³, Michael Soyka^{54

55}, Michael C Stallings^{9

56}, Michael Steffens⁵⁷, Jens Treutlein⁸, Ming Tsuang²³, Tamara L Wall²³, Norbert Wodarz⁵⁰, Vadim Yuferov⁴⁰, Peter Zill⁵⁸, Andrew W Bergen³², Jingchun Chen⁶, Paul M Cinciripini¹⁸, Howard J Edenberg⁵⁹, Marissa A Ehringer^{9

10}, Robert E Ferrell⁶⁰, Joel Gelernter^{20

61

62}, David Goldman¹⁹, John K Hewitt^{9

56}, Christian J Hopfer⁶³, William G Iacono¹⁵, Jaakko Kaprio^{13

14

64}, Mary Jeanne Kreek⁴⁰, Ivo M Kremensky²², Pamela A F Madden⁴, Matt McGue¹⁵, Marcus R Munafò⁶⁵, Robert A Philibert⁶⁶, Marcella Rietschel⁸, Alec Roy⁶⁷, Dan Rujescu¹², Sirkku T Saarikoski¹³, Gary E Swan⁶⁸, Alexandre A Todorov⁴, Michael M Vanyukov⁴⁹, Robert B Weiss⁶⁹, Laura J Bierut⁴, Nancy L Saccone⁷⁰

Affiliations

¹ Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA.
² 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.
³ 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.
⁴ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁵ Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁶ Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
⁷ Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA.
⁸ Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
⁹ Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USA.
¹⁰ Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA.
¹¹ Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, USA.
¹² Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
¹³ Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland.
¹⁴ Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
¹⁵ Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA.
¹⁶ Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
¹⁷ Oregon Research Institute, Eugene, OR, 97403, USA.
¹⁸ Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁹ Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
²⁰ Department of Psychiatry, Yale University, New Haven, CT, 06516, USA.
²¹ Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, United Kingdom.
²² Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria.
²³ Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
²⁴ Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany.
²⁵ Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
²⁶ Ökumenisches Hainich-Klinikum, Mühlhausen/Thüringen, Germany.
²⁷ National Drug and Alcohol Research Centre, University of New South Wales, Randwick, NSW, 2031, Australia.
²⁸ School of Population and Global Health, University of Melbourne, Melbourne, 3010, Australia.
²⁹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
³⁰ University of Düsseldorf, 40225, Düsseldorf, Germany.
³¹ Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
³² Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
³³ Institute of Behavioral Science, University of Colorado, Boulder, CO, 80309, USA.
³⁴ Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.
³⁵ Behavioral Health Research Division, Research Triangle Institute International, Durham, NC, 27709, USA.
³⁶ Department of Oncology, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
³⁷ Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
³⁸ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
³⁹ Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA.
⁴⁰ Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USA.
⁴¹ Addictions Department, Institute of Psychiatry, King's College London, London, SE5 8BB, UK.
⁴² University of Bonn, 53113, Bonn, Germany.
⁴³ Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
⁴⁴ Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, 4029, Australia.
⁴⁵ Harvard School of Public Health, Boston, MA, 02115, USA.
⁴⁶ Aarhus University, Aarhus, 8000, Denmark.
⁴⁷ Childhood Cancer Research Group, University of Oxford, Oxford, OX3 7LG, UK.
⁴⁸ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
⁴⁹ Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁵⁰ Department of Psychiatry, University Medical Center Regensburg, University of Regensburg, 8548, Regensburg, Germany.
⁵¹ Psychiatric Hospital, Konigsfelden, Windisch, Switzerland.
⁵² Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, USA.
⁵³ Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
⁵⁴ Department of Psychiatry, University of Munich, 3860, Munich, Germany.
⁵⁵ Private Hospital Meiringen, Meiringen, Switzerland.
⁵⁶ Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, 80309, USA.
⁵⁷ Research Department, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
⁵⁸ University of Munich, Munich, Germany.
⁵⁹ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
⁶⁰ Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
⁶¹ Department of Genetics, Yale University, New Haven, CT, 06516, USA.
⁶² Department of Neurobiology, Yale University, New Haven, CT, 06516, USA.
⁶³ Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
⁶⁴ Institute for Molecular Medicine FIMM, University of Helsinki, 00014, Helsinki, Finland.
⁶⁵ MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, and School of Experimental Psychology, University of Bristol, Bristol, BS8 1TU, UK.
⁶⁶ Department of Psychiatry, University of Iowa, Iowa City, IA, 52242, USA.
⁶⁷ Psychiatry Service, Department of Veteran Affairs, New Jersey VA Health Care System, East Orange, NJ, 07018, USA.
⁶⁸ Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, 94304, USA.
⁶⁹ Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.
⁷⁰ Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA. nlims@genetics.wustl.edu.

PMID: 26392368
PMCID: PMC4752855
DOI: 10.1007/s10519-015-9737-3

Meta-Analysis

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

Tae-Hwi Schwantes-An et al. Behav Genet. 2016 Mar.

. 2016 Mar;46(2):151-69.

doi: 10.1007/s10519-015-9737-3. Epub 2015 Sep 21.

Authors

Affiliations

¹ Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA.
² 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.
³ 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.
⁴ Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁵ Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA.
⁶ Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 23298, USA.
⁷ Department of Psychiatry, University of Utah School of Medicine, Salt Lake City, UT, 84108, USA.
⁸ Department of Genetic Epidemiology in Psychiatry, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
⁹ Institute for Behavioral Genetics, University of Colorado, Boulder, CO, 80309, USA.
¹⁰ Department of Integrative Physiology, University of Colorado, Boulder, CO, 80309, USA.
¹¹ Department of Biobehavioral Health, The Pennsylvania State University, University Park, PA, 16802, USA.
¹² Department of Psychiatry, Universitätsklinikum Halle (Saale), 06112, Halle (Saale), Germany.
¹³ Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, 00271, Finland.
¹⁴ Department of Public Health, University of Helsinki, Helsinki, 00014, Finland.
¹⁵ Department of Psychology, University of Minnesota, Minneapolis, MN, 55455, USA.
¹⁶ Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, 21205, USA.
¹⁷ Oregon Research Institute, Eugene, OR, 97403, USA.
¹⁸ Department of Behavioral Science, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
¹⁹ Section of Human Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20892, USA.
²⁰ Department of Psychiatry, Yale University, New Haven, CT, 06516, USA.
²¹ Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, United Kingdom.
²² Department of Medical Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, 1431, Sofia, Bulgaria.
²³ Department of Psychiatry, University of California San Diego, La Jolla, CA, 92093, USA.
²⁴ Department. of Genomics, Life and Brain Center, Institute of Human Genetics, University of Bonn, Bonn, 53127, Germany.
²⁵ Division of Medical Genetics, Department of Biomedicine, University Hospital Basel, University of Basel, Basel, 4003, Switzerland.
²⁶ Ökumenisches Hainich-Klinikum, Mühlhausen/Thüringen, Germany.
²⁷ National Drug and Alcohol Research Centre, University of New South Wales, Randwick, NSW, 2031, Australia.
²⁸ School of Population and Global Health, University of Melbourne, Melbourne, 3010, Australia.
²⁹ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
³⁰ University of Düsseldorf, 40225, Düsseldorf, Germany.
³¹ Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.
³² Center for Health Sciences, Biosciences Division, SRI International, Menlo Park, CA, 94025, USA.
³³ Institute of Behavioral Science, University of Colorado, Boulder, CO, 80309, USA.
³⁴ Max-Planck-Institute of Psychiatry, 80804, Munich, Germany.
³⁵ Behavioral Health Research Division, Research Triangle Institute International, Durham, NC, 27709, USA.
³⁶ Department of Oncology, University of Oxford, Oxford, OX3 7DQ, United Kingdom.
³⁷ Department of Addictive Behavior and Addiction Medicine, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
³⁸ Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.
³⁹ Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, CO, 80309, USA.
⁴⁰ Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, 10065, USA.
⁴¹ Addictions Department, Institute of Psychiatry, King's College London, London, SE5 8BB, UK.
⁴² University of Bonn, 53113, Bonn, Germany.
⁴³ Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, 68159, Mannheim, Germany.
⁴⁴ Department of Genetic Epidemiology, Queensland Institute of Medical Research, Brisbane, QLD, 4029, Australia.
⁴⁵ Harvard School of Public Health, Boston, MA, 02115, USA.
⁴⁶ Aarhus University, Aarhus, 8000, Denmark.
⁴⁷ Childhood Cancer Research Group, University of Oxford, Oxford, OX3 7LG, UK.
⁴⁸ Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
⁴⁹ Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA, 15213, USA.
⁵⁰ Department of Psychiatry, University Medical Center Regensburg, University of Regensburg, 8548, Regensburg, Germany.
⁵¹ Psychiatric Hospital, Konigsfelden, Windisch, Switzerland.
⁵² Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, 47405, USA.
⁵³ Addiction Research Group at the Department of Psychiatry and Psychotherapy, LVR Hospital Essen, University of Duisburg-Essen, 45147, Essen, Germany.
⁵⁴ Department of Psychiatry, University of Munich, 3860, Munich, Germany.
⁵⁵ Private Hospital Meiringen, Meiringen, Switzerland.
⁵⁶ Department of Psychology & Neuroscience, University of Colorado, Boulder, CO, 80309, USA.
⁵⁷ Research Department, Federal Institute for Drugs and Medical Devices (BfArM), Kurt-Georg-Kiesinger-Allee 3, 53175, Bonn, Germany.
⁵⁸ University of Munich, Munich, Germany.
⁵⁹ Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
⁶⁰ Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, 15261, USA.
⁶¹ Department of Genetics, Yale University, New Haven, CT, 06516, USA.
⁶² Department of Neurobiology, Yale University, New Haven, CT, 06516, USA.
⁶³ Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, 80045, USA.
⁶⁴ Institute for Molecular Medicine FIMM, University of Helsinki, 00014, Helsinki, Finland.
⁶⁵ MRC Integrative Epidemiology Unit, UK Centre for Tobacco and Alcohol Studies, and School of Experimental Psychology, University of Bristol, Bristol, BS8 1TU, UK.
⁶⁶ Department of Psychiatry, University of Iowa, Iowa City, IA, 52242, USA.
⁶⁷ Psychiatry Service, Department of Veteran Affairs, New Jersey VA Health Care System, East Orange, NJ, 07018, USA.
⁶⁸ Department of Medicine, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA, 94304, USA.
⁶⁹ Department of Human Genetics, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA.
⁷⁰ Department of Genetics, Washington University School of Medicine, 4523 Clayton Avenue, Campus Box 8232, St. Louis, MO, 63110, USA. nlims@genetics.wustl.edu.

PMID: 26392368
PMCID: PMC4752855
DOI: 10.1007/s10519-015-9737-3

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.

Keywords: Addiction; Genetic association; OPRM1; Opioid receptor; Single nucleotide polymorphism (SNP); Substance dependence.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr. Bierut is listed as an inventor on Issued U.S. Patent 8,080,371, “Markers for Addiction” covering the used of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction, and served as a consultant for Pfizer in 2008. Dr. NL Saccone is the spouse of Dr. SF Saccone, who is also listed as an inventor on the above patent. Dr. Cinciripini served on the scientific advisory board of Pfizer, conducted educational talks sponsored by Pfizer on smoking cessation (2006–2008), and has received grant support from Pfizer. Dr. Degenhardt has no relevant disclosures for this specific project; however, for general pharmaceutical company disclosures, Dr. Degenhardt has received untied educational grants from Reckitt Benckiser to conduct post-marketing surveillance of the diversion and injection of opioid substitution therapy medications in Australia. Although these activities are unrelated to the current study, Dr. Kranzler has been a consultant or advisory board member for Alkermes, Lilly, Lundbeck, Otsuka and Pfizer; he is also a member of the American Society of Clinical Psychopharmacology's Alcohol Clinical Trials Initiative, which is supported by Ethypharm, Lilly, Lundbeck, AbbVie, and Pfizer. Dr. Ridinger is member of the advisory board of Lundbeck referring to Nalmefene. Prof. Dr. N. Scherbaum received honoraria for several activities (advisory boards, lectures, manuscripts and educational material) by the factories Sanofi-Aventis, Reckitt-Benckiser, Lundbeck, and Janssen-Cilag. During the last three years he participated in clinical trials financed by the pharmaceutical industry. The remaining authors declare no conflict of interest.

Figures

**Figure 1**
Forest plot of general substance dependence and rs1799971 across studies that had at least 5 cases and 5 controls. Summary odds ratio, 95% Confidence Interval, and p-values are based on fixed effect meta-analysis. *indicates the subset of 10 studies that had all five specific substance dependence diagnoses, examined in secondary analyses to confirm consistency of results. Estimated heterogeneity variance was Q = 20.13 with a p-value of 0.387 among all 20 studies and Q = 6.49 with a p-value of 0.69 among the subset of 10 studies.

**Figure 2**
Forest plot of general substance dependence and rs1799971 across studies that had at least 5 cases and 5 controls. Summary odds ratio, 95% Confidence Interval, and p-values are based on fixed effect meta-analysis. *indicates the subset of 10 studies that had all five specific substance dependence diagnoses, examined in secondary analyses to confirm consistency of results. Estimated heterogeneity variance was Q = 20.13 with a p-value of 0.387 among all 20 studies and Q = 6.49 with a p-value of 0.69 among the subset of 10 studies.

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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

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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

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