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

• Published in: Nature Genetics
• Main 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
• Other Authors: 1 deCODE Genet Amgen, Reykjavik, Iceland 2 Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands 3 Kings Coll London, St Thomas Hosp, Dept Twin Res, London, England 4 Erasmus MC, Dept Internal Med, Rotterdam, Netherlands 5 Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece 6 Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Biostat, London, England 7 Integrated Res Dev Determinants Ageing & Longev I, Leiden, Netherlands 8 Netherlands Consortium Hlth Ageing, Leiden, Netherlands 9 Arctic Mass, Reykjavik, Iceland 10 Univ Iceland, Fac Med, Reykjavik, Iceland 11 Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands 12 Univ Oxford, Biomed Res Unit, NIHR, Oxford, England 13 Akureyri Hosp, Dept Orthoped Surg, Akureyri, Iceland 14 Univ Akureyri, Inst Hlth Sci, Akureyri, Iceland 15 Lund Univ, Dept Orthoped, Lund, Sweden 16 Leiden Univ, Med Ctr, Dept Clin Epidemiol, Leiden, Netherlands 17 Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands 18 Leiden Univ, Med Ctr, Dept Orthopaed, Leiden, Netherlands 19 Univ Nottingham, City Hosp Nottingham, Acad Rheumatol, Nottingham NG7 2RD, England 20 Natl Univ Hosp Iceland, Dept Med, Reykjavik, Iceland
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature 2014
• Subjects: Base Sequence; Cartilage; Chromosomes; Human; Pair 1; Computational Biology; Gene Expression Profiling; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Variation; Genotype; Great Britain; Hand; Humans; Iceland; Molecular Sequence Data; Netherlands; Osteoarthritis; Retinal Dehydrogenase; Sequence Analysis; DNA
• Online Access: http://hdl.handle.net/2336/324975; https://doi.org/10.1038/ng.2957

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field. 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). info:eu-repo/grantAgreement/EC/FP7/200800