Advanced

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

Styrkarsdottir, Unnur; Thorleifsson, Gudmar; Helgadottir, Hafdis T; Bomer, Nils; Metrustry, Sarah; Bierma-Zeinstra, S; Strijbosch, Annelieke M; Evangelou, Evangelos; Hart, Deborah and Beekman, Marian, et al. (2014) In Nature Genetics 46(5). p.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... (More)
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). (Less)
Please use this url to cite or link to this publication:
author
, et al. (More)
(Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
46
issue
5
pages
498 - 502
publisher
Nature Publishing Group
external identifiers
  • pmid:24728293
  • wos:000335422900019
  • scopus:84899638695
ISSN
1546-1718
DOI
10.1038/ng.2957
language
English
LU publication?
yes
id
76bf7c1c-6b48-4efa-a3b0-ed3e3e571331 (old id 4430149)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24728293?dopt=Abstract
date added to LUP
2014-05-05 20:22:41
date last changed
2017-11-12 03:13:13
@article{76bf7c1c-6b48-4efa-a3b0-ed3e3e571331,
  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).},
  author       = {Styrkarsdottir, Unnur and Thorleifsson, Gudmar and Helgadottir, Hafdis T and Bomer, Nils and Metrustry, Sarah and Bierma-Zeinstra, S and Strijbosch, Annelieke M and Evangelou, Evangelos and Hart, Deborah and Beekman, Marian and Jonasdottir, Aslaug and Sigurdsson, Asgeir and Eiriksson, Finnur F and Thorsteinsdottir, Margret and Frigge, Michael L and Kong, Augustine and Gudjonsson, Sigurjon A and Magnusson, Olafur T and Masson, Gisli and Hofman, Albert and Arden, Nigel K and Ingvarsson, Thorvaldur and Lohmander, Stefan and Kloppenburg, Margreet and Rivadeneira, Fernando and Nelissen, Rob G H H and Spector, Tim and Uitterlinden, Andre and Slagboom, P Eline and Thorsteinsdottir, Unnur and Jonsdottir, Ingileif and Valdes, Ana M and Meulenbelt, Ingrid and van Meurs, Joyce and Jonsson, Helgi and Stefansson, Kari},
  issn         = {1546-1718},
  language     = {eng},
  number       = {5},
  pages        = {498--502},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {Severe osteoarthritis of the hand associates with common variants within the ALDH1A2 gene and with rare variants at 1p31.},
  url          = {http://dx.doi.org/10.1038/ng.2957},
  volume       = {46},
  year         = {2014},
}