title: A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: the Treat-OA consortium.
abstract: To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genome-wide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81x10(-5)). The C allele conferred a reduced risk of 33% to 41% using a case-control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA.
authors.affiliation: Department of Twin Research & Genetic Epidemiology, King's College London, UK. guangju.zhai@kcl.ac.uk
authors.forename: G
authors.initials: G
authors.lastname: Zhai
authors.forename: J B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: G
authors.initials: G
authors.lastname: Livshits
authors.forename: I
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: A M
authors.initials: AM
authors.lastname: Valdes
authors.forename: N
authors.initials: N
authors.lastname: Soranzo
authors.forename: D
authors.initials: D
authors.lastname: Hart
authors.forename: F
authors.initials: F
authors.lastname: Zhang
authors.forename: B S
authors.initials: BS
authors.lastname: Kato
authors.forename: J B
authors.initials: JB
authors.lastname: Richards
authors.forename: F M K
authors.initials: FM
authors.lastname: Williams
authors.forename: M
authors.initials: M
authors.lastname: Inouye
authors.forename: M
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: P
authors.initials: P
authors.lastname: Deloukas
authors.forename: E
authors.initials: E
authors.lastname: Slagboom
authors.forename: A
authors.initials: A
authors.lastname: Uitterlinden
authors.forename: T D
authors.initials: TD
authors.lastname: Spector
mesh_terms: D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D006225:Hand; D006801:Humans; D008297:Male; D010003:Osteoarthritis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins