Abstract
Osteoarthritis (OA) is a prevalent, heritable degenerative joint disease with a substantial public health impact. We used a 1000-Genomes-Project-based imputation in a genome-wide association scan for osteoarthritis (3177 OA cases and 4894 controls) to detect a previously unidentified risk locus. We discovered a small disease-associated set of variants on chromosome 13. Through large-scale replication, we establish a robust association with SNPs in
MCF2L
(rs11842874, combined odds ratio [95% confidence interval] 1.17 [1.11–1.23], p = 2.1 × 10
−8
) across a total of 19,041 OA cases and 24,504 controls of European descent. This risk locus represents the third established signal for OA overall.
MCF2L
regulates a nerve growth factor (NGF), and treatment with a humanized monoclonal antibody against NGF is associated with reduction in pain and improvement in function for knee OA patients.