1 Department of Sports Science and Clinical Biomechanics, Det Sundhedsvidenskabelige Fakultet, SDU2 Musculoskeletal Function and Physiotherapy, Department of Sports Science and Clinical Biomechanics, Det Sundhedsvidenskabelige Fakultet, SDU3 Orthopaedics, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU4 deCODE Genetics/Amgen, Reykjavik, Iceland.5 Leiden University Medical Center6 King's College London7 Erasmus Medical Center8 1] Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece.  Department of Epidemiology and Biostatistics, Imperial College London, London, UK.9 Arctic Mass, Reykjavik, Iceland.10 University of Iceland11 University of Oxford12 1] Department of Orthopedic Surgery, Akureyri Hospital, Akureyri, Iceland.  Institution of Health Science, University of Akureyri, Akureyri, Iceland.13 unknown14 Orthopaedics, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
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).
Nature Genetics, 2014, Vol 46, Issue 5, p. 498-502
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