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Chunk #17 — RESULTS — Opioid Dependence vs. Exposed and Unexposed Controls

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Leveraging genome-wide data to investigate differences between opioid use vs. opioid dependence in 41,176 individuals from the Psychiatric Genomics Consortium.
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In the ODexposed analysis, which is the comparison most relevant to dependence liability given exposure but also the one that most constricted the sample size, no association survived the genome-wide significance threshold (p=5×10–8). Additionally, there were no significant enrichments for GO annotations, molecular pathways, nor tissue-specific regulation. The ODunexposed comparison identified a GWS association in the African-ancestry meta-analysis, rs201123820 on chromosome 18 (z=5.55, p=2.9×10–8; Figure 1A; Table 1; see Supplementary Table 5 for ancestry-specific results for each genome-wide significant variant). With respect to this locus, no heterogeneity was observed among the cohorts included in the meta-analysis (heterogeneity: I2=0, p=0.473; Supplementary Table 6). This variant did not show significant genetic associations with traits related to other addictive substances (Supplementary Table 3). The gene-based association analysis identified a GWS gene in the same genomic region, C18orf32 (p=1.8×10–6; Table 1; Supplementary Figure 1A). Additionally, in the African-ancestry meta-analysis, we also observed an enrichment for adipose tissue (beta=0.04, p=4.21×10–4; Figure 2A) and GO:0034498 – early endosome to Golgi transport (beta=1.01, p=5.1×10–8). In the trans-ancestry meta-analysis, we observed significant enrichment for specific adult stages of