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

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... Mehr ...

Verfasser: 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
Dokumenttyp: Artikel
Erscheinungsdatum: 2014
Verlag/Hrsg.: Nature
Schlagwörter: 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
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-29179103
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : http://hdl.handle.net/2336/324975

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