Journal
BEHAVIOR GENETICS
Volume 46, Issue 2, Pages 151-169Publisher
SPRINGER
DOI: 10.1007/s10519-015-9737-3
Keywords
Addiction; Substance dependence; OPRM1; Opioid receptor; Single nucleotide polymorphism (SNP); Genetic association
Funding
- National Institute on Drug Abuse (NIDA) [R01 DA026911]
- NIDA [R01 DA018823, R01 DA021905, R01 AA017889, P60 DA011015, R01 DA012845, T32 DA017637, R01 DA021913, K24 DA032555, K01 AA019447, R01 DA035804]
- NIAAA [U10 AA008401, R01 AA009367, R01 AA0011886, R01 AA075356, R01 AA07728, R01 AA13220, R01 AA13321, R01 AA13322, R01 AA11998, R01 AA17688, R01 AA017535, R01 AA11330]
- Australian National Health and Medical Research Council (NHMRC) [1041472]
- Australian Government under Substance Misuse Prevention and Service Improvements Grant Fund
- NCI
- Genes and Environment Initiative (GEI) [U01 HG004438]
- National Institutes of Health (NIH) [HHSN268200782096C]
- National Cancer Institute (NCI)
- NIH [HHSN268200782096C]
- Finnish National Institute for Health and Welfare
- National Institute on Alcohol Abuse and Alcoholism (NIAAA) [K02 AA018755, R01 AA-09203, R37 AA-12502, 141054, 263278]
- Academy of Finland [213506, 129680]
- GRAND (Kaprio) from Pfizer Inc.
- European Union [Health-F4-2007-201413]
- ENGAGE project from NIDA [DA12854]
- Wellcome Trust Sanger Institute
- Sigrid Juselius Foundation
- Jenny AMP
- Antti Wihuri Foundation
- German Federal Ministry of Education and Research (BMBF) [01EB0410, 01GS0852, BMBF 01ZX1311A]
- National Genome Research Network (NGFN Plus) [FZK 01GS08152]
- Alfried Krupp von Bohlen und Halbach-Stiftung
- Adelson Medical Research Foundation
- National Institute of Mental Health (NIMH) [R01 MH066140]
- NARSAD: The Brain and Behavior Research Foundation
- Sidney R. Baer, Jr. Foundation
- Gerber Foundation
- Australian National Health and Medical Research Council
- Cancer Research UK [C53/A6281]
- British Heart Foundation
- Cancer Research UK
- Economic and Social Research Council
- Medical Research Council
- National Institute for Health Research under UK Clinical Research Collaboration
- University of California Tobacco-Related Disease Research Program [7PT2000-2004]
- NHLBI
- NARSAD: the Brain and Behavior Research Fund
- Division of Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health
- The NIDA [R01 DA026911, P01 CA089392, K08 DA030398, K08 DA032680, R01 DA038076, R21 DA038241, R01 DA036583, R01 DA015789, P50 DA05130, R01 DA005147, R01 DA036216, R01 U01 DA024417, R01 DA012846, R01 DA12690, R01 DA12849, R01 DA18432, K01 DA24758]
- NIDA. [R01 DA017305, R01 DA019157, P50 DA005605, R01 DA011922, R01 DA11822, K07 CA92209, R21 CA81649, P50 CA070907, R01 DA019963, R01 DA013423, RC2 DA028793K08 DA019951R01 DA003706 U01 DA020830 P01 HL72903DA019498R01 DA18673RC2 DA028909]
- [1 X01 HG005274-01]
- [U01 HG004446]
- MRC [MC_UU_12013/6] Funding Source: UKRI
- Lundbeck Foundation [R155-2014-1724] Funding Source: researchfish
- Medical Research Council [MR/K023195/1, MC_UU_12013/6] Funding Source: researchfish
Ask authors/readers for more resources
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. a parts per thousand currency sign10). 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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