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

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 var...

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Bibliographic Details
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
Format: Article in Journal/Newspaper
Language:English
Published: 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:https://portal.findresearcher.sdu.dk/da/publications/5c04f060-ac72-472e-a31a-787af4e7c685
https://doi.org/10.1038/ng.2957
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Summary: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).

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