Our findings show, for the first time, that OPRM1 intron 1 contains SNPs that have replicable associations with heroin addiction. Our findings further suggest that rs3778150 and possibly other intron 1 SNPs may tag a cis-eQTL that influences OPRM1 expression and underlies the disease associations. Our tested SNPs also included rs563649, which is located in intron 1 and was previously reported for being associated with OPRM1 expression in vitro (64); we did not corroborate this association with OPRM1 expression (smallest P=0.26, Table S5) and did not find evidence for association with heroin addiction in our discovery cohort (meta-analysis P=0.57). Fine-mapping in the intron 1 region, particularly in diverse ancestry groups with varied linkage disequilibrium patterns, is needed to delineate the variants that influence both OPRM1 expression and heroin addiction.
