title: A meta-analysis of European and Asian cohorts reveals a global role of a functional SNP in the 5' UTR of GDF5 with osteoarthritis susceptibility.
abstract: We have performed a meta-analysis combining data for more than 11,000 individuals. It provides compelling evidence for a positive association between a functional single-nucleotide polymorphism (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) of 1.10. Although 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.
authors.affiliation: Institute of Musculoskeletal Sciences, Botnar Research Centre, Nuffield Orthopaedic Centre, University of Oxford, Oxford, UK.
authors.forename: Kay
authors.initials: K
authors.lastname: Chapman
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takahashi
authors.forename: Ingrid
authors.initials: I
authors.lastname: Meulenbelt
authors.forename: Chris
authors.initials: C
authors.lastname: Watson
authors.forename: Julio
authors.initials: J
authors.lastname: Rodriguez-Lopez
authors.forename: Rainer
authors.initials: R
authors.lastname: Egli
authors.forename: Aspasia
authors.initials: A
authors.lastname: Tsezou
authors.forename: Konstantinos N
authors.initials: KN
authors.lastname: Malizos
authors.forename: Margreet
authors.initials: M
authors.lastname: Kloppenburg
authors.forename: Dongquan
authors.initials: D
authors.lastname: Shi
authors.forename: Lorraine
authors.initials: L
authors.lastname: Southam
authors.forename: Ruud
authors.initials: R
authors.lastname: van der Breggen
authors.forename: Rachelle
authors.initials: R
authors.lastname: Donn
authors.forename: Jianghui
authors.initials: J
authors.lastname: Qin
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
authors.forename: P Eline
authors.initials: PE
authors.lastname: Slagboom
authors.forename: Gillian
authors.initials: G
authors.lastname: Wallis
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kamatani
authors.forename: Qing
authors.initials: Q
authors.lastname: Jiang
authors.forename: Antonio
authors.initials: A
authors.lastname: Gonzalez
authors.forename: John
authors.initials: J
authors.lastname: Loughlin
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics*; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D015331:Cohort Studies; D004198:Disease Susceptibility / Q000503:physiopathology*; D005260:Female; D005787:Gene Frequency; D005799:Genes, Dominant; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D055428:Growth Differentiation Factor 5; D006801:Humans; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5