| Literature DB >> 24728293 |
Unnur Styrkarsdottir1, Gudmar Thorleifsson1, Hafdis T Helgadottir1, Nils Bomer2, Sarah Metrustry3, S Bierma-Zeinstra4, Annelieke M Strijbosch2, Evangelos Evangelou5, Deborah Hart3, Marian Beekman6, Aslaug Jonasdottir1, Asgeir Sigurdsson1, Finnur F Eiriksson7, Margret Thorsteinsdottir8, Michael L Frigge1, Augustine Kong1, Sigurjon A Gudjonsson1, Olafur T Magnusson1, Gisli Masson1, Albert Hofman9, Nigel K Arden10, Thorvaldur Ingvarsson11, Stefan Lohmander12, Margreet Kloppenburg13, Fernando Rivadeneira14, Rob G H H Nelissen15, Tim Spector3, Andre Uitterlinden14, P Eline Slagboom6, Unnur Thorsteinsdottir16, Ingileif Jonsdottir16, Ana M Valdes17, Ingrid Meulenbelt18, Joyce van Meurs4, Helgi Jonsson19, Kari Stefansson16.
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).Entities:
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Year: 2014 PMID： 24728293 DOI： 10.1038/ng.2957
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330