The GWS gene-based association of OA with FURIN was driven by a single variant, rs17514846. However, this signal was supported by analysis of additional FURIN variants in a subset of cohorts where more FURIN variants were available, including a GWS association with OA at the variant level for rs11372849. FURIN is a member of the convertase family and encodes a type 1 membrane bound protease that is expressed in neuroendocrine and brain tissues, among others (https://www.ncbi.nlm.nih.gov/gene/5045). Although FURIN shows higher expression across brain tissues than OPRM1, the S-PrediXcan analysis did not show significant predicted genetically driven expression differences associated with OA for this gene, and the highest posterior probabilities from the colocalization analysis favored no association of either eQTLs or the OA-variant association signal at this locus. However, this may reflect the single variant association with OA in the gSEM GWAS and an effect on OA through mechanisms other than gene expression.
