A Variant in MCF2L Is Associated with Osteoarthritis

作者：Aaron Day-Williams, Lorraine Southam, Kalliope Panoutsopoulou, Nigel William Rayner, Tõnu Esko, Karol Estrada, Hafdis Th. Helgadottir, Albert Hofman, T. Ingvarsson, Helgi Jónsson, Aime Keis, Hanneke J. M. Kerkhof, Guðmar Þorleifsson, Nigel K. Arden, Andrew D Carr, Kay E. Chapman, Panos Deloukas, John A. Loughlin, Andrew W. McCaskie, William Ollier, Stuart H. Ralston, Timothy D. Spector, Gillian A. Wallis, Jeremy Mark Wilkinson, Nadim Aslam, F Birell, Ian Carluke, John Joseph, Ashok Rai, Mike R. Reed, Kirsten Walker, Sally A. Doherty, Ingileif Jónsdóttir, Rose A. Maciewicz, Kenneth Ross Muir, Andres Metspalu, Fernando Rivadeneira, Kāri Stefánsson, Unnur Styrkársdóttir, André Gerardus Uitterlinden, Joyce B. J. van Meurs, Weiya Zhang, Ana Maria Valdes, Michael Doherty, Eleftheria Zeggini · 发表于：The American Journal of Human Genetics · 年份：2011 · DOI：10.1016/j.ajhg.2011.08.001 · 被引用次数：150 · 研究领域：Osteoarthritis Treatment and Mechanisms、Peroxisome Proliferator-Activated Receptors、Genetic Associations and Epidemiology

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.