A novel variant in GLIS3 is associated with osteoarthritis

摘要: Objectives Osteoarthritis (OA) is a complex disease, but its genetic aetiology remains poorly characterised. To identify novel susceptibility loci for OA, we carried out genome-wide association study (GWAS) in individuals from the largest UK-based OA collections to date. Methods We discovery GWAS 5414 with knee and/or hip total joint replacement (TJR) and 9939 population-based controls. followed-up prioritised variants subjects interim release of UK Biobank resource (up 12 658 cases 50 898 controls) our lead finding operated full (17 894 89 470 controls). investigated functional implications methylation, gene expression proteomics data primary chondrocytes 12 pairs intact degraded cartilage samples patients undergoing TJR. Results detect significant at rs10116772 TJR (P=3.7×10 −8 ; allele A: OR (95% CI) 0.97 (0.96 0.98)), an intronic variant GLIS3 , which expressed cartilage. Variants strong correlation have been associated elevated plasma glucose levels diabetes. Conclusions locus that has previously implicated diabetes glycaemic traits.