| Literature DB >> 21871595 |
Aaron G Day-Williams1, Lorraine Southam, Kalliope Panoutsopoulou, Nigel W Rayner, Tonu Esko, Karol Estrada, Hafdis T Helgadottir, Albert Hofman, Throvaldur Ingvarsson, Helgi Jonsson, Aime Keis, Hanneke J M Kerkhof, Gudmar Thorleifsson, Nigel K Arden, Andrew Carr, Kay Chapman, Panos Deloukas, John Loughlin, Andrew McCaskie, William E R Ollier, Stuart H Ralston, Timothy D Spector, Gillian A Wallis, J Mark Wilkinson, Nadim Aslam, Fraser Birell, Ian Carluke, John Joseph, Ashok Rai, Mike Reed, Kirsten Walker, Sally A Doherty, Ingileif Jonsdottir, Rose A Maciewicz, Kenneth R Muir, Andres Metspalu, Fernando Rivadeneira, Kari Stefansson, Unnur Styrkarsdottir, Andre G Uitterlinden, Joyce B J van Meurs, Weiya Zhang, Ana M Valdes, Michael Doherty, Eleftheria Zeggini.
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.Entities:
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Year: 2011 PMID： 21871595 PMCID： PMC3169824 DOI： 10.1016/j.ajhg.2011.08.001
Source DB: PubMed Journal: Am J Hum Genet ISSN： 0002-9297 Impact factor: 11.025