西亚试剂：Variant in MCF2L Is Associated with Osteoarthritis

A Variant in MCF2L Is Associated with Osteoarthritis

Aaron G. Day-Williams1, Lorraine Southam1, 2, Kalliope Panoutsopoulou1, Nigel W. Rayner2, Tonu Esko3, 4, 5, Karol Estrada6, 7, Hafdis T. Helgadottir8, Albert Hofman9, Throvaldur Ingvarsson10, 11, Helgi Jonsson11, 12, Aime Keis13, 14, Hanneke J.M. Kerkhof6, 7, Gudmar Thorleifsson8, Nigel K. Arden15, 16, Andrew Carr17, Kay Chapman17, Panos Deloukas1, John Loughlin18, Andrew McCaskie18, 19, William E.R. Ollier20, Stuart H. Ralston21, Timothy D. Spector22, Gillian A. Wallis23, J. Mark Wilkinson24, 25, Nadim Aslam26, Fraser Birell18, 27, Ian Carluke27, John Joseph28, Ashok Rai29, Mike Reed27, Kirsten Walker27, arcOGEN Consortium, Sally A. Doherty30, Ingileif Jonsdottir8, 11, Rose A. Maciewicz31, Kenneth R. Muir32, Andres Metspalu3, 4, 5, Fernando Rivadeneira6, 7, 9, Kari Stefansson8, 11, Unnur Styrkarsdottir8, Andre G. Uitterlinden6, 7, 9, Joyce B.J. van Meurs6, 7, Weiya Zhang30, Ana M. Valdes22, Michael Doherty30 and Eleftheria Zeggini1

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.