Letters

Osteoarthritis of the knee is a major cause of pain, disability and the use of healthcare resources among middle-aged and older people. 1 Although osteoarthritis is multifactorial, it is known to have a signifi cant genetic contribution and a number of studies have attempted to dissect such a contribution (see Valdes and Spector 2 for review). The GDF5 gene encodes the growth differentiation factor 5, a bone morphogenetic protein involved in joint formation, expressed in different joint structures, which has been shown to ameliorate tendon, ligament and bone healing after trauma in mice. 3 4 A promoter polymorphism (rs143383) in GDF5 has been found to be strongly associated with both hip and knee osteoar-thritis in Asian individuals, 4 and is the most widely replicated genetic association with knee osteoarthritis, although much less so for hip and hand osteoarthritis. 5 This variant is functional, with the lower gene expression variant having increased genetic risk. 4 A large-scale meta-analysis reported the association of the major (T) allele with knee osteoarthritis achieved OR 1.15 p=9.7×10 −7 and achieved p=9×10 −5 (OR 1.13, 95 % CI 1.06 to 1.20) when Asian subjects were excluded. 5 The genome-wide statistical signifi cance level of p<5×10 −8 is increasingly seen as the threshold at which genetic associations are considered credible. 6 The aim of our study was to prove that common genetic variation in the GDF5 gene is important in knee osteoarthritis beyond reasonable doubt. We genotyped 3303 controls and 2235 knee osteoarthriti