Cindy Boer

Genetics of Osteoarthritis Consortium GWAS Meta-Analyses | 179 4.1 Lead OA SNV Coding Variant & Fine- map FineMapped Gene eQTL colocalization (Gtex/OA tissue) Cartilage Subchon- dral Bone Blood pQTL MR CoLoc musculoskeletal phenotype Score Gene Druggable Genome Diff. Expresion Diff. Abundance Diff. Expresion Mouse Human rs67924081 LTBP3(1/1) LTBP3 (+) LTBP3 LTBP3 5 LTBP3 Tier 3A rs7212908 TBX4 (-) TBX4 TBX4 3 TBX4 . rs72760655 COL27A1 (-) COL27A1 COL27A1 3 COL27A1 Tier 3A rs7294636 MGP(4/2) MGP MGP MGP 5 MGP Tier 3B rs75621460 TGFB1 TGFB1 TGFB1 3 TGFB1 Tier 1 rs7581446 LTBP1 LTBP1(1/0) LTBP1 3 LTBP1 Tier 3A rs76340814 PTCH1(5/2) PTCH1 3 PTCH1 . rs7967762 COL2A1(1/0) COL2A1 COL2A1 3 COL2A1 Tier 3A rs7967762 PFKM(2/2) PFKM (-) PFKM 4 PFKM . rs7967762 WNT10B (+) WNT10B (+) WNT10B WNT10B 4 WNT10B Tier 3B rs9396861 RNF144B RNF144B(2/1) 3 RNF144B . rs9981408 ERG ERG(1/1) ERG 4 ERG Tier 2 Table 3 : Gene s are identified according to the Ensembl GeneName for the gene. Abbreviations are: Lead OA SNV, rsid of the lead variant; EA, effect allele: EAF effect allele frequency; OA, if the signal is new (N) or previously reported (K); Coding variant & FineMap, gene in which the lead SNV has a moderate to high severity or gene in which a moderate to high severity variant* is in high LD (≥r20.8) with the lead SNV and is present in the 95% credible set; Fine mapped gene, all variants in the 95% credible set reside within the transcript of this gene. eQTL colocalisation, gene was colocalised in at least 1 GTEx tissue with the number of GTEx tissues in parentheses followed by the number of these tissues that were also enriched in tissue enrichment analysis , which is suggestive of a role in osteoarthritis pathology. Cartilage Differential Expr, Gene was differentially expressed in high-grade compared to low-grade osteoarthritic cartilage; Cartilage Differential Abund, gene that codes for a protein that was differentially expressed in high-grade compared to low-grade osteoarthritic cartilage. Bone Differen- tial Expr, Gene was differentially expressed in high-grade compared to low-grade in sub-chondral bone; Blood pQTL MR Coloc, gene that was identified as on the causal path in the mendelian randomisation for cis-eQTLs and also colocalised; Score, cumulative score for each gene based on the supporting Finemap and functional analysis;Human musculoskeletal phenotype, indicates if a gene has been linked to a musculoskeletal phenotype according to the Nosology and classification of genetic skeletal disorders (PMID: 31633310); Mouse musculoskeletal phenotype, indicates if a musculoskeletal phenotype is observed in any mouse knockout from www.boneandcartilage.com and the MGI (Mouse Genome Informatics Database) Batch Query was used to extract all mouse knockout phenotypes from the GDX (Mouse Gene Expression Database) we used the Nosology and classification of genetic skeletal disorders (PMID: 31633310) to identify genes within 1Mb (upstream or down- stream) of the 100 SNVs that had links to human musculosketal phenotypes: *Moderate to high consequences for severity: transcript_ablation, splice_acceptor, splice_donor, stop_gained, frameshift, stop_lost, start_lost, transcript_am- plification, inframe_insertion, inframe_deletion, missense, protein_altering Table 3 (continued): Possible Causal Osteoarthritis Genes