To estimate the likelihood that the genetic loci associated with OA share a causal variant with the expression quantitative trait loci (eQTLs) for our nominated genes (OPRM1, PPP6C, and FURIN), we applied coloc43 to our gSEM GWAS results and the GTEx eQTL results for these genes. Because the variants underlying the GWS association for PPP6C physically extend into SCAI and RABEPK (Supplementary Fig. 14), we included these genes in the analysis. We evaluated colocalization across the superset of 10 brain tissues which showed genetically driving differential expression for at least one gene in the S-PrediXcan analysis (Supplementary Table 14). OPRM1 is expressed at relatively low levels in the GTEx brain tissues (Supplementary Fig. 17a). Only six of 10 brain tissues showed variant associations with OPRM1 expression in GTEx and could be included in the coloc analysis. The posterior probabilities for four tissues of the six tissues tested for OPRM1 favored the hypothesis that only a genetic association with OA at this locus is present (Fig. 5H2, Supplementary Table 15). However, in the cerebellum, where OPRM1 is most highly expressed and
