The gene-level association between FURIN and OA was based on a single variant (rs17514846-A, beta = − 0.08, p = 8.82 × 10–7). While other FURIN variants were available in individual cohorts, the gSEM GWAS, and thereby the MAGMA analysis, included only one due to the gSEM method’s requirement that variants be present in every contributing cohort. A standard logistic regression meta-analysis of FURIN variants across the subset of GWAS cohorts without overlapping participants (GENOA, MVP, and PH) retained additional variants excluded from the gSEM analysis and identified 3 additional variants in strong LD with rs17514846 (r2 > 0.64, D’ = 1.0); all four variants were associated with OA (Supplementary Fig. 15; Supplementary Table 13), the weakest association being for rs17514846 (p = 1.67 × 10–6) and the strongest being for rs11372849, which was GWS (rs11372849-TC, beta = -0.074, p = 4.11 × 10–8; forest plot Supplementary Fig. 16).
