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

dc.contributor.authorStyrkarsdottir, Unnur
dc.contributor.authorThorleifsson, Gudmar
dc.contributor.authorHelgadottir, Hafdis T
dc.contributor.authorBomer, Nils
dc.contributor.authorMetrustry, Sarah
dc.contributor.authorBierma-Zeinstra, S
dc.contributor.authorStrijbosch, Annelieke M
dc.contributor.authorEvangelou, Evangelos
dc.contributor.authorHart, Deborah
dc.contributor.authorBeekman, Marian
dc.contributor.authorJonasdottir, Aslaug
dc.contributor.authorSigurdsson, Asgeir
dc.contributor.authorEiriksson, Finnur F
dc.contributor.authorThorsteinsdottir, Margret
dc.contributor.authorFrigge, Michael L
dc.contributor.authorKong, Augustine
dc.contributor.authorGudjonsson, Sigurjon A
dc.contributor.authorMagnusson, Olafur T
dc.contributor.authorMasson, Gisli
dc.contributor.authorHofman, Albert
dc.contributor.authorArden, Nigel K
dc.contributor.authorIngvarsson, Thorvaldur
dc.contributor.authorLohmander, Stefan
dc.contributor.authorKloppenburg, Margreet
dc.contributor.authorRivadeneira, Fernando
dc.contributor.authorNelissen, Rob G H H
dc.contributor.authorSpector, Tim
dc.contributor.authorUitterlinden, Andre
dc.contributor.authorSlagboom, P Eline
dc.contributor.authorThorsteinsdottir, Unnur
dc.contributor.authorJonsdottir, Ingileif
dc.contributor.authorValdes, Ana M
dc.contributor.authorMeulenbelt, Ingrid
dc.contributor.authorvan Meurs, Joyce
dc.contributor.authorJonsson, Helgi
dc.contributor.authorStefansson, Kari
dc.date.accessioned2014-08-19T14:57:19Z
dc.date.available2014-08-19T14:57:19Z
dc.date.issued2014-05
dc.date.submitted2014-08-19
dc.identifier.citationNat. Genet. 2014, 46(5):498-502en
dc.identifier.issn1546-1718
dc.identifier.pmid24728293
dc.identifier.doi10.1038/ng.2957
dc.identifier.urihttp://hdl.handle.net/2336/324975
dc.descriptionTo access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.en
dc.description.abstractOsteoarthritis 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).
dc.description.sponsorshipinfo:eu-repo/grantAgreement/EC/FP7/200800en
dc.language.isoenen
dc.publisherNatureen
dc.relationinfo:eu-repo/grantAgreement/EC/FP7/200800en
dc.relation.urlhttp://www.nature.com/ng/journal/v46/n5/full/ng.2957.htmlen
dc.relation.urlhttp://dx.doi.org/10.1038/ng.2957en
dc.rightsopenAccessen
dc.subject.meshBase Sequenceen
dc.subject.meshCartilageen
dc.subject.meshChromosomes, Human, Pair 1en
dc.subject.meshComputational Biologyen
dc.subject.meshGene Expression Profilingen
dc.subject.meshGenetic Association Studiesen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenetic Variationen
dc.subject.meshGenotypeen
dc.subject.meshGreat Britainen
dc.subject.meshHanden
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshNetherlandsen
dc.subject.meshOsteoarthritisen
dc.subject.meshRetinal Dehydrogenaseen
dc.subject.meshSequence Analysis, DNAen
dc.titleSevere osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.en
dc.typeArticleen
dc.contributor.department[ 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, Icelanden
dc.identifier.journalNature geneticsen
dc.rights.accessLandspitali Access - LSH-aðganguren
html.description.abstractOsteoarthritis 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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