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Lookup NU author(s): Dr Kaye Chapman, Arata Takahashi, Dr Catherine Watson, Professor John LoughlinORCiD
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We have performed a meta-analysis combining data for over 11,000 individuals. It provides compelling evidence for a positive association between a functional SNP in the 5' UTR of GDF5 (+104T/C; rs143383) and osteoarthritis (OA) in European and Asian populations. This SNP has recently been reported to be associated with OA in Japanese and Han Chinese populations. Attempts to replicate this association in European samples have been inconclusive as no association was found in the case-control cohorts from the UK, Spain and Greece when studied individually. However, the pooled data of UK and Spain found an association of the T-allele with an odds ratio (OR) 1.10. Whilst the European studies had adequate power to replicate the original findings from the Japanese cohort (OR = 1.79), these results suggest that the role of the GDF5 polymorphism may not be as strong in Europeans. To clarify whether the European studies were hampered by insufficient power we combined new data from the UK and the Netherlands with the three published studies of Europe and Asia. The results provide strong evidence of a positive association of the GDF5 SNP with knee OA for Europeans as well as for Asians. The combined association for both ethnic groups is highly significant for the allele frequency model (P = 0.0004, OR = 1.21) and the dominant model (P <0.0001, OR = 1.48). These findings represent the first highly significant evidence for a risk factor for the development of OA which affects two highly diverse ethnic groups.
Author(s): Chapman K, Takahashi A, Meulenbelt I, Watson C, Rodriguez-Lopez J, Egli R, Tsezou A, Malizos KN, Kloppenburg M, Shi D, Southam L, Breggen Rvander, Donn R, Qin J, Doherty M, Slagboom PE, Wallis G, Kamatani N, Jiang Q, Gonzalez A, Loughlin J, Ikegawa S
Publication type: Article
Publication status: Published
Journal: Human Molecular Genetics
Year: 2008
Volume: 17
Issue: 10
Pages: 1497-504
ISSN (print): 0964-6906
ISSN (electronic): 1460-2083
Publisher: Oxford University Press
URL: http://dx.doi.org/10.1093/hmg/ddn038
DOI: 10.1093/hmg/ddn038
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