Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1
Dana B Hancock1, Joshua L Levy2, Nathan C Gaddis2
1Behavioral Health Epidemiology Program, Behavioral Health and Criminal Justice Division, Research Triangle Institute (RTI) International, St. Louis, Missouri..
Biological Psychiatry
|March 7, 2015
Summary
Common OPRM1 gene variations in intron 1 are linked to heroin addiction risk. These findings clarify the role of OPRM1 single nucleotide polymorphisms (SNPs) in opioid addiction, particularly rs3778150.
Area of Science:
- Genetics
- Neuroscience
- Pharmacogenomics
Background:
- The opioid receptor, mu 1 (OPRM1) gene is a plausible candidate for opioid addiction due to its role in pain and reward pathways.
- Previous studies have yielded inconsistent results regarding the association between OPRM1 gene polymorphisms, including the functional single nucleotide polymorphism (SNP) rs1799971, and heroin addiction.
Purpose of the Study:
- To investigate the association between OPRM1 gene single nucleotide polymorphisms (SNPs) and heroin addiction.
- To identify specific OPRM1 SNPs that influence OPRM1 gene expression and confer risk for heroin addiction.
Main Methods:
- Tested 103 OPRM1 SNPs for association with OPRM1 messenger RNA expression in human prefrontal cortex.
- Evaluated 16 cis-expression quantitative trait loci (cis-eQTL) SNPs for association with heroin addiction across three cohorts (totaling 16,729 individuals).
Main Results:
- Four cis-eQTL SNPs, including rs3778150 in OPRM1 intron 1, showed significant association with heroin addiction.
- Rs3778150-C allele was associated with increased heroin addiction risk (meta-analysis p = 4.3 × 10(-8)).
- The functional SNP rs1799971-A showed association with heroin addiction only in the presence of the rs3778150-C allele.
Conclusions:
- Common OPRM1 intron 1 SNPs demonstrate replicable associations with heroin addiction.
- The haplotype structure involving rs3778150 and nearby SNPs may explain inconsistent findings for rs1799971 in prior studies.
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