Journal
MOLECULAR PSYCHIATRY
Volume 26, Issue 7, Pages 3169-3177Publisher
SPRINGERNATURE
DOI: 10.1038/s41380-020-00902-4
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Funding
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
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The study aimed to determine the genetic background of the OPRM1 region 118G and its potential modulatory effect. Seven common haplotypes with distinct population distribution were identified, with some containing additional regulatory SNPs that may modulate the effect of 118G. Further analysis revealed specific genetic backgrounds in different populations, highlighting the need for specific experimental approaches to differentiate between the effects of 118G and other SNPs.
The mu-opioid receptor (MOR,OPRM1) has important roles in diverse functions including reward, addiction, and response to pain treatment. SNP rs1799971 (118A > G, N40D) which occur at a high frequency (40-60%) in Asia and moderate frequency (15%) in samples of European ancestry, is the only common coding variant in the canonical transcript, in non-African populations. Despite extensive studies, the molecular consequences of this variation remained unresolved. The aim of this study was to determine the genetic background of theOPRM1region of 118G in four representative populations and to assess its potential modulatory effect. Seven common haplotypes with distinct population distribution were identified based on seven SNPs. Three haplotypes carry the 118G and additional highly linked regulatory SNPs (e.g., rs9383689) that could modulate the effect of 118G. Extended analysis in the 1000 Genomes database (n = 2504) revealed a common East Asian-specific haplotype with a different genetic background in which there are no variant alleles for an upstream LD block tagged by the eQTL rs9397171. The major European haplotype specifically includes the eQTL intronic SNP rs62436463 that must have arisen after the split between European and Asian populations. Differentiating between the effect of 118G and these SNPs requires specific experimental approaches. The analysis also revealed a significant increase in two 118A haplotypes with eQTL SNPs associated with drug addiction (rs510769) and obesity (rs9478496) in populations with native Mexican ancestry. Future studies are required to assess the clinical implication of these findings.
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