Multi-trait genome-wide association study of opioid addiction: OPRM1 and beyond
Nathan Gaddis1, Ravi Mathur1, Jesse Marks1
1GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
Scientific Reports
|October 7, 2022
Summary
Genetic studies reveal new insights into opioid addiction (OA) heritability. Researchers identified novel genetic associations with OPRM1, PPP6C, and FURIN, advancing our understanding of OA
Area of Science:
- Genetics
- Psychiatry
- Pharmacogenomics
Background:
- Opioid addiction (OA) exhibits moderate heritability, but genetic underpinnings remain incompletely understood.
- Only one variant, rs1799971 (A118G) in OPRM1, has been genome-wide significant for OA.
- Previous studies lacked the scale to fully explore the genetic architecture of OA.
Purpose of the Study:
- To conduct a large-scale genome-wide association study (GWAS) for opioid addiction.
- To identify novel genetic loci associated with OA and explore pleiotropy.
- To refine understanding of the genetic basis of opioid addiction.
Main Methods:
- Genomic structural equation modeling was applied to a large meta-analysis dataset.
- Combined data from the Genetics of Opioid Addiction Consortium (GENOA), Psychiatric Genomics Consortium, Million Veteran Program, and Partners Health.
- Analysis included 23,367 cases and an effective sample size of 88,114 individuals of European ancestry.
Main Results:
- Strongest evidence to date for OPRM1 association with OA, led by SNP rs9478500 (p=2.56×10⁻⁹).
- Novel genome-wide significant associations identified for PPP6C and FURIN gene loci.
- High genetic correlations (r_g > 0.9) observed across various OA phenotypes.
Conclusions:
- This study provides the most robust genetic evidence to date for OPRM1's role in opioid addiction.
- Identified PPP6C and FURIN as novel loci contributing to OA susceptibility.
- Findings suggest pleiotropic effects of these variants across addiction and related traits, paving the way for future research.
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