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.

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Persistent URL dx.doi.org/10.1016/j.ajhg.2011.08.001, hdl.handle.net/1765/33289
Day-Williams, A.G, Southam, L, Panoutsopoulou, K, Rayner, N.W, Esko, T, Estrada Gil, K, … Zeggini, E. (2011). A variant in MCF2L is associated with osteoarthritis. American Journal of Human Genetics, 89(3), 446–450. doi:10.1016/j.ajhg.2011.08.001