A Variant in MCF2L Is Associated with Osteoarthritis

AG Day-Williams, L Southam, K Panoutsopoulou, NW Rayner, T Esko, Karol Estrada Gil, HT Helgadottir, Bert Hofman, T Ingvarsson, H Jonsson, A Keis, HJM Kerkhof, G Thorleifsson, NK Arden, A Carr, K Chapman, P Deloukas, J Loughlin, A McCaskie, WER OllierSH Ralston, TD Spector, GA Wallis, JM Wilkinson, N Aslam, F Birell, I Carluke, J Joseph, A Rai, M Reed, K Walker, SA Doherty, I Jonsdottir, RA Maciewicz, KR Muir, A Metspalu, Fernando Rivadeneira, K Stefansson, U Styrkarsdottir, André Uitterlinden, Joyce van Meurs, WY Zhang, AM Valdes, M Doherty, E Zeggini

Research output: Contribution to journalArticleAcademicpeer-review

110 Citations (Scopus)

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 x 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.
Original languageEnglish
Pages (from-to)446-450
Number of pages5
JournalAmerican Journal of Human Genetics
Volume89
Issue number3
DOIs
Publication statusPublished - 2011

Research programs

  • EMC MM-01-25-01
  • EMC MM-01-39-09-A
  • EMC NIHES-01-64-01

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