| Literature DB >> 26392368 |
Tae-Hwi Schwantes-An1,2, Juan Zhang1,3, Li-Shiun Chen4, Sarah M Hartz4, Robert C Culverhouse5, Xiangning Chen6, Hilary Coon7, Josef Frank8, Helen M Kamens9,10,11, Bettina Konte12, Leena Kovanen13, Antti Latvala14, Lisa N Legrand15, Brion S Maher16, Whitney E Melroy9,10, 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 Cichon24,25, Robin P Corley9, Norbert Dahmen26, Louisa Degenhardt27,28, Tatiana Foroud29, Wolfgang Gaebel30, Ina Giegling12, Stephen J Glatt31, Richard A Grucza4, Jill Hardin32, Annette M Hartmann12, Andrew C Heath4, Stefan Herms24,25, Colin A Hodgkinson19, Per Hoffmann24,25, Hyman Hops17, David Huizinga33, Marcus Ising34, Eric O Johnson35, Elaine Johnstone36, Radka P Kaneva22, Kenneth S Kendler6, Falk Kiefer37, Henry R Kranzler38, Ken S Krauter9,39, Orna Levran40, Susanne Lucae34, Michael T Lynskey41, Wolfgang Maier42, Karl Mann43, Nicholas G Martin44, Manuel Mattheisen24,45,46, Grant W Montgomery44, Bertram Müller-Myhsok34, Michael F Murphy47, Michael C Neale6, Momchil A Nikolov4,22, Denise Nishita32, Markus M Nöthen24, John Nurnberger48, Timo Partonen13, Michele L Pergadia4, Maureen Reynolds49, Monika Ridinger50,51, Richard J Rose52, Noora Rouvinen-Lagerström13, Norbert Scherbaum53, Christine Schmäl43, Michael Soyka54,55, Michael C Stallings9,56, 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 Ehringer9,10, Robert E Ferrell60, Joel Gelernter20,61,62, David Goldman19, John K Hewitt9,56, Christian J Hopfer63, William G Iacono15, Jaakko Kaprio13,14,64, 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.
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.Entities:
Keywords: Addiction; Genetic association; OPRM1; Opioid receptor; Single nucleotide polymorphism (SNP); Substance dependence
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Year: 2015 PMID： 26392368 PMCID： PMC4752855 DOI： 10.1007/s10519-015-9737-3
Source DB: PubMed Journal: Behav Genet ISSN： 0001-8244 Impact factor: 2.805