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Chunk #16 — Results — Testing cis-eQTL SNPs for association with heroin addiction

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Cis-Expression Quantitative Trait Loci Mapping Reveals Replicable Associations with Heroin Addiction in OPRM1.
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The 16 putative cis-eQTL SNPs for OPRM1 were tested for association with heroin addiction in UHS cases vs. population controls (Figure 1 and Table 1). There was no evidence to suggest heterogeneity for any of the 16 SNPs (smallest P=0.15), and the imputation quality of all tested SNPs was high (info>0.9). Meta-analysis across the ancestry groups revealed 4 SNPs significantly associated with heroin addiction at P<0.005, based on an overall α=0.05 corrected for 10 independent tests among the 16 cis-eQTL SNPs (35, 36): rs9478495, rs3778150, rs9384169, and rs562859. Minor alleles of these four SNPs were common (frequencies ranging from 16% to 38%), and they had consistent directions of association: odds ratios (ORs) ranging from 1.12 to 1.28 across the ancestry groups. The two most significantly associated SNPs for heroin addiction (rs9478495 and rs3778150) were in moderate linkage disequilibrium in the 1000 Genomes EUR panel (r2=0.48, Figure S3A) but weak linkage disequilibrium in the AFR panel (r2=0.04, Figure S3B).