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.
نویسندگان
چکیده
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.
منابع مشابه
Author’s response to reviews Title: Lack of Association of the Opioid Receptor mu 1 (OPRM1) A118G Polymorphism (rs1799971) with Alcohol Dependence: Review and Meta-analysis of Retrospective Controlled Studies
Title: Lack of Association of the Opioid Receptor mu 1 (OPRM1) A118G Polymorphism (rs1799971) with Alcohol Dependence: Review and Meta-analysis of Retrospective Controlled Studies Authors: Xiangyi Kong ([email protected]) Hao Deng ([email protected]) Shun Gong ([email protected]) Theodore Alston ([email protected]) Yanguo Kong ([email protected]) Jingping Wang ...
متن کاملAssociation of opioid receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) with nicotine dependence
Background and Object Whether opioid-receptor mu 1 (OPRM1) A118G polymorphism (rs1799971) is associated with nicotine dependence is controversial. We analyzed the combined results from published studies of this possibility. Methods Literature reviews were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Web of Science, Chinese Nati...
متن کاملCis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1.
BACKGROUND No opioid receptor, mu 1 (OPRM1) gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, have been conclusively associated with heroin/other opioid addiction, despite their biological plausibility. We used evidence of polymorphisms altering OPRM1 expression in normal human brain tissue to nominate and then test associations with heroin addiction. ...
متن کاملA cis-eQTL in OPRM1 is Associated with Subjective Response to Alcohol and Alcohol Use.
BACKGROUND A functional polymorphism within the μ-opioid receptor (OPRM1) gene, rs1799971 (A118G), previously has been associated with measures of alcohol use and sensitivity to its effects, but findings have been inconclusive. A recent study suggested that a second nearby variant within OPRM1, rs3778150, is robustly associated with heroin dependence and fully explained a smaller observed assoc...
متن کاملµ-Opioid Receptor Gene (OPRM1) Polymorphism A118G: Lack of Association in Finnish Populations with Alcohol Dependence or Alcohol Consumption
AIMS The molecular epidemiological studies on the association of the opioid receptor µ-1 (OPRM1) polymorphism A118G (Asn40Asp, rs1799971) and alcohol use disorders have given conflicting results. The aim of this study was to test the possible association of A118G polymorphism and alcohol use disorders and alcohol consumption in three large cohort-based study samples. METHODS The association b...
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عنوان ژورنال:
- Behavior genetics
دوره 46 2 شماره
صفحات -
تاریخ انتشار 2016