Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.

To access publisher's full text version of this article click on the hyperlink belowOsteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.Wellcome Trust NIHR Cambridge Biomedical Research Centre Erasmus Medical Center Erasmus University Organization for Health Research and Development (ZonMw) Netherlands Genomics Initiative (NGI)/Netherlands Organisation of Scientific Research (NWO) Netherlands Consortium for Healthy Aging (NCHA) Research Institute for Diseases in the Elderly (RIDE) Ministry of Education, Culture and Science Ministry for Health, Welfare and Sports European Commission (DG XII) Municipality of Rotterda