Fig 6 |. Multiple lines of evidence support PAPPA as an OA risk gene.

The matrix metalloproteinase PAPPA has previously been found to have increased expression in OA tissue. (A) A boxplot depicting increased PAPPA log2 normalized expression counts in response to FN-f treatment (log2 fold change = 3.14). (B) PAPPA shows increased expression in older donors. Star indicates significance (adjusted p-value < 0.05). (C) The OA risk allele (C, bolded) of variant rs1321917 is associated with higher expression of PAPPA in chondrocytes in both PBS (blue) and FN-f (yellow). (D) The colocalized PBS eQTL signal for PAPPA does not overlap with the promoter or the gene body but is connected to the promoters via a 420 Kb chromatin loop which supports this distal eQTL. Total Hip Replacement GWAS is colored by LD relative to the GWAS index rs1321917 according to the 1000 Genomes European reference panel. Gray bars highlight the genomic regions of loop anchors.