Gene level analyses of gSEM GWAS results using MAGMA41 showed significant associations with OPRM1 and two novel genes out of 15,977 genes tested (p < 3.13 × 10–6; Fig. 4; Q-Q plot Supplementary Fig. 13; full results in Supplementary Table 12). These novel gene-based associations include Protein Phosphatase 6 Catalytic subunit gene (PPP6C) and Furin Paired Basic Amino Acid Cleaving Enzyme gene (FURIN). The association between PPP6C and OA utilized 57 variants including several in LD that approached variant-level genome-wide significance (p = 3.37 × 10–7 to 2.14 × 10–5, Fig. 1b). This peak extended across three genes: PPP6C, SCAI, and RABEPK (Supplementary Fig. 14) but only PPP6C reached gene-based genome-wide significance (SCAI p = 0.0016; RABEPK p = 2.82 × 10–5).
