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.
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.
Zhai
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Department of Twin Research & Genetic Epidemiology, King's College London, UK. guangju.zhai@kcl.ac.uk
van Meurs
J B J
JB
Livshits
G
G
Meulenbelt
I
I
Valdes
A M
AM
Soranzo
N
N
Hart
D
D
Zhang
F
F
Kato
B S
BS
Richards
J B
JB
Williams
F M K
FM
Inouye
M
M
Kloppenburg
M
M
Deloukas
P
P
Slagboom
E
E
Uitterlinden
A
A
Spector
T D
TD
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*
C455479:RBFOX1 protein, human; D000072260:RNA Splicing Factors; D016601:RNA-Binding Proteins