Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.

Nat Genet 2014 May 13;46(5):498-502. Epub 2014 Apr 13.

1] deCODE Genetics/Amgen, Reykjavik, Iceland. [2] Faculty of Medicine, University of Iceland, Reykjavik, Iceland.

Osteoarthritis is the most common form of arthritis and is a major cause of pain and disability in the elderly. To search for sequence variants that confer risk of osteoarthritis of the hand, we carried out a genome-wide association study (GWAS) in subjects with severe hand osteoarthritis, using variants identified through the whole-genome sequencing of 2,230 Icelanders. We found two significantly associated loci in the Icelandic discovery set: at 15q22 (frequency of 50.7%, odds ratio (OR) = 1.51, P = 3.99 × 10(-10)) in the ALDH1A2 gene and at 1p31 (frequency of 0.02%, OR = 50.6, P = 9.8 × 10(-10)). Among the carriers of the variant at 1p31 is a family with several members in whom the risk allele segregates with osteoarthritis. The variants within the ALDH1A2 gene were confirmed in replication sets from The Netherlands and the UK, yielding an overall association of OR = 1.46 and P = 1.1 × 10(-11) (rs3204689).

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http://dx.doi.org/10.1038/ng.2957DOI Listing
May 2014
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References

(Supplied by CrossRef)

RF Loeser et al.
Arthritis Rheum. 2012

H Jonsson et al.
Arthritis Rheum. 2003

TD Spector et al.
Osteoarthritis Cartilage 2004

VB Kraus et al.
Osteoarthritis Cartilage 2007

IK Haugen et al.
Ann. Rheum. Dis. 2011

HJ Kerkhof et al.
Arthritis Rheum. 2010

E Evangelou et al.
Ann. Rheum. Dis. 2011

AG Day-Williams et al.
Am. J. Hum. Genet. 2011

MC Castaño Betancourt et al.
Proc. Natl. Acad. Sci. USA 2012

Y Miyamoto et al.
Nat. Genet. 2008

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