This study provides an unequivocal GWS association signal for the intron 1 locus in OPRM1 and, through haplotype analysis, suggests that rs1799971 (A118G) may not be the driver of the locus’s association with OA. We also identified two novel GWS gene-based associations with OA: PPP6C and FURIN. Both genes have been previously associated with phenotypes correlated with OA (e.g. PPP6C with cigarette smoking31,32, alcohol consumption31, and depressive symptoms33; FURIN with schizophrenia34,35, risk tolerance36, and insomnia36). This study links these genes to predicted genetically driven differential expression in brain tissues by OA. Colocalization analysis supports a shared single variant between OA association and gene expression for PPP6C but the results for OPRM1 and FURIN are not as well defined. Collectively, these results provide extended insight into the association of OPRM1 with OA and implicate novel genes associated with this phenotype.
