Osteoarthritis is the most common form of arthritis and has a huge clinical and economic impact. The disease has a complex aetiology but genetic factors play an important role in pathogenesis. Identification of the loci that predispose to OA susceptibility will lead to a much better understanding of the cause of the disease as well as identifying new molecular targets for therapeutic intervention. Alleles that predispose to OA could also be used, in individual cases, to determine prognosis and the response to surgical or drug treatments. Recent advances in human molecular genetics coupled with the HapMap project and the development of relatively low cost high-throughput genotyping platforms provides us now with an opportunity to comprehensively search the whole genome for OA risk alleles. The aim of this proposal is to conduct a genome-wide association study for OA susceptibility alleles in a large collaborative study of 8000 OA cases and 6000 controls involving 5 UK centres. We will scan the human genome for associated variants using a cohort of 4000 OA cases and 3000 controls and then replicate associated loci using an independent cohort of 4000 cases and 3000 controls. Our application is timely, in that it exploits the latest developments in the genetics of complex traits, and is unique, in that it represents the first genome-wide association scan for this common arthritis. The idea and design of the study originated at the Department of Twin Research.