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

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Authors
Styrkarsdottir, Unnur
Thorleifsson, Gudmar
Helgadottir, Hafdis T
Bomer, Nils
Metrustry, Sarah
Bierma-Zeinstra, S
Strijbosch, Annelieke M
Evangelou, Evangelos
Hart, Deborah
Beekman, Marian
Jonasdottir, Aslaug
Sigurdsson, Asgeir
Eiriksson, Finnur F
Thorsteinsdottir, Margret
Frigge, Michael L
Kong, Augustine
Gudjonsson, Sigurjon A
Magnusson, Olafur T
Masson, Gisli
Hofman, Albert
Arden, Nigel K
Ingvarsson, Thorvaldur
Lohmander, Stefan
Kloppenburg, Margreet
Rivadeneira, Fernando
Nelissen, Rob G H H
Spector, Tim
Uitterlinden, Andre
Slagboom, P Eline
Thorsteinsdottir, Unnur
Jonsdottir, Ingileif
Valdes, Ana M
Meulenbelt, Ingrid
van Meurs, Joyce
Jonsson, Helgi
Stefansson, Kari
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Issue Date
2014-05

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Citation
Nat. Genet. 2014, 46(5):498-502
Abstract
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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Additional Links
http://www.nature.com/ng/journal/v46/n5/full/ng.2957.html
http://dx.doi.org/10.1038/ng.2957
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openAccess
ae974a485f413a2113503eed53cd6c53
10.1038/ng.2957
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