We applied S-PrediXcan42 using GTEx version 8 eQTL gene models (http://predictdb.org/) with the gSEM GWAS summary statistics as input to estimate genetically driven differential gene expression in human brain tissues associated with OA. Fourteen gene-tissue combinations surpassed correction for the total number of gene models and brain tissues (156,215 tests) with a false discovery rate (FDR) less than 0.05 (Table 1; all results presented in Supplementary Table 14). Predicted genetically driven OPRM1 expression was significantly associated with OA in cerebellum. Only four brain tissues had gene models for OPRM1 (cerebellum, cerebellar hemisphere, hypothalamus, and nucleus accumbens; Supplementary Table 14). In contrast, PPP6C was predicted to be differentially expressed in nine of 12 available brain tissue models. Nearby SCAI was the only other gene to show statistically significant genetically driven expression associated with OA, doing so across four brain tissues. FURIN was nominally associated (p = 9.67 × 10–5) in hippocampus but did not surpass the FDR < 0.05 threshold. RABEPK was not predicted to be differentially expressed by OA (best p = 0.055 in caudate).Table 1Fourteen gene-brain region combinations exhibiting
