A Variant in MCF2L Is Associated with Osteoarthritis

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• 作者：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 ; Eleftheria Zeggini¹ ;   ; ^{eleftheria@sanger.ac.uk}
• 刊名：The American Journal of Human Genetics
• 出版年：2011
• 出版时间：9 September 2011
• 年：2011
• 卷：89
• 期：3
• 页码：446-450
• 全文大小：444 K

文摘

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?.23], p?=?2.1?¡Á 10^?) 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.