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Addiction, substance dependence, OPRM1, opioid receptor, single nucleotide polymorphism (SNP), genetic association
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. 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.
