title: A variant in MCF2L is associated with osteoarthritis.
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.
authors.affiliation: Wellcome Trust Sanger Institute, Hinxton, UK.
authors.forename: Aaron G
authors.initials: AG
authors.lastname: Day-Williams
authors.forename: Lorraine
authors.initials: L
authors.lastname: Southam
authors.forename: Kalliope
authors.initials: K
authors.lastname: Panoutsopoulou
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Rayner
authors.forename: Tonu
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authors.lastname: Esko
authors.forename: Karol
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authors.lastname: Estrada
authors.forename: Hafdis T
authors.initials: HT
authors.lastname: Helgadottir
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Throvaldur
authors.initials: T
authors.lastname: Ingvarsson
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authors.initials: H
authors.lastname: Jonsson
authors.forename: Aime
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authors.lastname: Keis
authors.forename: Hanneke J M
authors.initials: HJ
authors.lastname: Kerkhof
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Nigel K
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authors.lastname: Arden
authors.forename: Andrew
authors.initials: A
authors.lastname: Carr
authors.forename: Kay
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authors.lastname: Chapman
authors.forename: Panos
authors.initials: P
authors.lastname: Deloukas
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
authors.forename: Andrew
authors.initials: A
authors.lastname: McCaskie
authors.forename: William E R
authors.initials: WE
authors.lastname: Ollier
authors.forename: Stuart H
authors.initials: SH
authors.lastname: Ralston
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Spector
authors.forename: Gillian A
authors.initials: GA
authors.lastname: Wallis
authors.forename: J Mark
authors.initials: JM
authors.lastname: Wilkinson
authors.forename: Nadim
authors.initials: N
authors.lastname: Aslam
authors.forename: Fraser
authors.initials: F
authors.lastname: Birell
authors.forename: Ian
authors.initials: I
authors.lastname: Carluke
authors.forename: John
authors.initials: J
authors.lastname: Joseph
authors.forename: Ashok
authors.initials: A
authors.lastname: Rai
authors.forename: Mike
authors.initials: M
authors.lastname: Reed
authors.forename: Kirsten
authors.initials: K
authors.lastname: Walker
authors.forename: Sally A
authors.initials: SA
authors.lastname: Doherty
authors.forename: Ingileif
authors.initials: I
authors.lastname: Jonsdottir
authors.forename: Rose A
authors.initials: RA
authors.lastname: Maciewicz
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Muir
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
authors.forename: Unnur
authors.initials: U
authors.lastname: Styrkarsdottir
authors.forename: Andre G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Weiya
authors.initials: W
authors.lastname: Zhang
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Zeggini
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D020932:Nerve Growth Factor / Q000276:immunology / Q000378:metabolism; D016017:Odds Ratio; D010003:Osteoarthritis / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D064067:Rho Guanine Nucleotide Exchange Factors; D044465:White People / Q000235:genetics
chemical_list: D000911:Antibodies, Monoclonal; D020662:Guanine Nucleotide Exchange Factors; C577400:MCF2L protein, human; D064067:Rho Guanine Nucleotide Exchange Factors; D020932:Nerve Growth Factor