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, T. H. and Zhang, J. and Chen, L. S. and Hartz, S. M. and Culverhouse, R. C. and Chen, X. and Coon, H. and Frank, J. and Kamens, H. M. and Konte, B. and Kovanen, L. and Latvala, A. and Legrand, L. N. and Maher, B. S. and Melroy, W. E. and Nelson, E. C. and Reid, M. W. and Robinson, J. D. and Shen, P. H. and Yang, B. Z. and Andrews, J. A. and Aveyard, P. and Beltcheva, O. and Brown, S. A. and Cannon, D. S. and Cichon, S. and Corley, R. P. and Dahmen, N. and Degenhardt, L. and Foroud, T. and Gaebel, W. and Giegling, I. and Glatt, S. J. and Grucza, R. A. and Hardin, J. and Hartmann, A. M. and Heath, A. C. and Herms, S. and Hodgkinson, C. A. and Hoffmann, P. and Hops, H. and Huizinga, D. and Ising, M. and Johnson, E. O. and Johnstone, E. and Kaneva, R. P. and Kendler, K. S. and Kiefer, F. and Kranzler, H. R. and Krauter, K. S. and Levran, O. and Lucae, S. and Lynskey, M. T. and Maier, W. and Mann, K. and Martin, N. G. and Mattheisen, M. and Montgomery, G. W. and Muller-Myhsok, B. and Murphy, M. F. and Neale, M. C. and Nikolov, M. A. and Nishita, D. and Nothen, M. M. and Nurnberger, J. and Partonen, T. and Pergadia, M. L. and Reynolds, M. and Ridinger, M. and Rose, R. J. and Rouvinen-Lagerstrom, N. and Scherbaum, N. and Schmal, C. and Soyka, M. and Stallings, M. C. and Steffens, M. and Treutlein, J. and Tsuang, M. and Wall, T. L. and Wodarz, N. and Yuferov, V. and Zill, P. and Bergen, A. W. and Chen, J. and Cinciripini, P. M. and Edenberg, H. J. and Ehringer, M. A. and Ferrell, R. E. and Gelernter, J. and Goldman, D. and Hewitt, J. K. and Hopfer, C. J. and Iacono, W. G. and Kaprio, J. and Kreek, M. J. and Kremensky, I. M. and Madden, P. A. and McGue, M. and Munafo, M. R. and Philibert, R. A. and Rietschel, M. and Roy, A. and Rujescu, D. and Saarikoski, S. T. and Swan, G. E. and Todorov, A. A. and Vanyukov, M. M. and Weiss, R. B. and Bierut, L. J. and Saccone, N. L.. (2016) 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, 46 (2). pp. 151-169.

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Official URL: https://edoc.unibas.ch/61584/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:16 Apr 2019 15:53
Deposited On:16 Apr 2019 15:53

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