Cindy Boer

Cartilage Thickness and Hip Osteoarthritis | 77 2.1 Table 4: Prioritized genes for Osteoarthritis loci. Biological and database evidence was collected to identify the causal gene in each investigated osteoarthritis as- sociated locus. Locus gene sets were constructed by taking a region of 500 Kb upstream and 500Kb downstream of the lead SNP of that locus (1MB locus region), in total we analysed 289 genes. The tables gives a summary of the biological evidence for each osteoarthritis associated locus: 1) Nearest located genes 2) DEPICT gene prioritization results, only genes that were significantly prioritized (FDR <0.05) are listed 3) GRAIL results, only nominal significant results are listed (P<0.05) 4) Mouse cartilage or bone gene expression 5) bone or cartilage development phenotype in mouse. Mouse expression and phenotype data was obtained from the Jackson lab database (http://www.informatics.jax.org/). 6) Human cartilage tissue gene expression and 7) differential gene expression between OA cartilage tissue and Preserved cartilage tissue (Ramos et al., 2014,GEO series accession number: GSE57218) 8)OMIM phenotype 9) eQTL evidence (blood eQTL browser, and Westra et al) and 10) Nonsynonymous variants in LD >0.6 with lead SNP. All evidence for each gene is summarized, genes with the highest number of evidence are reported. rs10471753 rs10492367 rs10948155 rs11177 rs11880992 rs12206662 rs2236995 rs2862851 rs496547 rs6094710 rs788748 rs835487 Rr9350591 GWAS association mJSW HipOA mJSW TJR mJSW mJSW mJSW mJSW mJSW Hip OA HipOA THR Hip OA Nearest Genes PIK3R1 KLHL42 PTHLH CDC5LSUPT3H GNL3 DOT1L RUNX2 SLBP TGFα TRH DDX6 ZMYND8 NCOA3 IGFBP3 CHST11 FILIP1 SENP6 GRAIL Not Significant Not Significant Not Significant Not Significant Not Significant Not Significant Not Significant Not Significant SULF2 IGFBP3 Not Significant Not Significant GRAIL p-value 6.4x10 -03 2.4x10 -02 4.4x10 -03 DEPICT Gene PIK3R1 KLHL42 RUNX2 No prioritization Multiple genes prioritized RUNX2 No prioritization VAX2 UPK2 Multiple genes prioritized IGFBP3 CHST11 No prioritization DEPICT p-value 7.4x10 -05 5.0x10 -03 1.5x10 -03 1.5x10 -03 8.9x10 -04 3.81E -03 2.37E -03 1.04E -03 Mouse Gene - PTHLH RUNX2 BAP1 GADD45B RUNX2 FGFR3 TGFα KMT2A SULF2 IGFBP3 CHST11 COL12A1 Bone & Cartilage Expr. - + + + + + + + - + + + + Bone & Cartilage Phenotype - + + + - + + - + - + + + Human Gene PIK3R1 PTHLH RUNX2 GNL3 GADD45B RUNX2 FGFR3 TGFa - SULF2 NCOA3 IGFBP3 - COL12A1 Cartilage tissue expr. + + + + + + + + - + + - + Diff. expr. OA cartilage tissue PIK3R1 PTHLH - GNL3 GADD45B - FGFR3 TGFα Multiple genes NCOA3 IGFBP3 TXNRD1 COL12A1