OBJECTIVES: To replicate the possible genetic association between ankylosing spondylitis (AS) and TNFRSF1A. METHODS: TNFRSF1A was re-sequenced in 48 individuals with AS to identify novel polymorphisms. Nine single nucleotide polymorphisms (SNPs) in TNFRSF1A and 5 SNPs in the neighbouring gene SCNN1A were genotyped in 1604 UK Caucasian individuals with AS and 1019 matched controls. An extended study was implemented using additional genotype data on 8 of these SNPs from 1400 historical controls from the 1958 British Birth Cohort. A meta-analysis of previously published results was also undertaken. RESULTS: One novel variant in intron 6 was identified but no new coding variants. No definite associations were seen in the initial study but in the extended study there were weak associations with rs4149576 (p=0.04) and rs4149577 (p=0.007). In the meta-analysis consistent, somewhat stronger associations were seen with rs4149577 (p=0.002) and rs4149578 (p=0.006). CONCLUSIONS: These studies confirm the weak genetic associations between AS and TNFRSF1A. In view of the previously reported associations of TNFRSF1A with AS, in Caucasians and Chinese, and the biological plausibility of this candidate gene, replication of this finding in well powered studies is clearly indicated.
OBJECTIVES: To replicate the possible genetic association between ankylosing spondylitis (AS) and TNFRSF1A. METHODS: TNFRSF1A was re-sequenced in 48 individuals with AS to identify novel polymorphisms. Nine single nucleotide polymorphisms (SNPs) in TNFRSF1A and 5 SNPs in the neighbouring gene SCNN1A were genotyped in 1604 UK Caucasian individuals with AS and 1019 matched controls. An extended study was implemented using additional genotype data on 8 of these SNPs from 1400 historical controls from the 1958 British Birth Cohort. A meta-analysis of previously published results was also undertaken. RESULTS: One novel variant in intron 6 was identified but no new coding variants. No definite associations were seen in the initial study but in the extended study there were weak associations with rs4149576 (p=0.04) and rs4149577 (p=0.007). In the meta-analysis consistent, somewhat stronger associations were seen with rs4149577 (p=0.002) and rs4149578 (p=0.006). CONCLUSIONS: These studies confirm the weak genetic associations between AS and TNFRSF1A. In view of the previously reported associations of TNFRSF1A with AS, in Caucasians and Chinese, and the biological plausibility of this candidate gene, replication of this finding in well powered studies is clearly indicated.
Authors: Adrian Cortes; Johanna Hadler; Jenny P Pointon; Philip C Robinson; Tugce Karaderi; Paul Leo; Katie Cremin; Karena Pryce; Jessica Harris; Seunghun Lee; Kyung Bin Joo; Seung-Cheol Shim; Michael Weisman; Michael Ward; Xiaodong Zhou; Henri-Jean Garchon; Gilles Chiocchia; Johannes Nossent; Benedicte A Lie; Øystein Førre; Jaakko Tuomilehto; Kari Laiho; Lei Jiang; Yu Liu; Xin Wu; Linda A Bradbury; Dirk Elewaut; Ruben Burgos-Vargas; Simon Stebbings; Louise Appleton; Claire Farrah; Jonathan Lau; Tony J Kenna; Nigil Haroon; Manuel A Ferreira; Jian Yang; Juan Mulero; Jose Luis Fernandez-Sueiro; Miguel A Gonzalez-Gay; Carlos Lopez-Larrea; Panos Deloukas; Peter Donnelly; Paul Bowness; Karl Gafney; Hill Gaston; Dafna D Gladman; Proton Rahman; Walter P Maksymowych; Huji Xu; J Bart A Crusius; Irene E van der Horst-Bruinsma; Chung-Tei Chou; Raphael Valle-Oñate; Consuelo Romero-Sánchez; Inger Myrnes Hansen; Fernando M Pimentel-Santos; Robert D Inman; Vibeke Videm; Javier Martin; Maxime Breban; John D Reveille; David M Evans; Tae-Hwan Kim; Bryan Paul Wordsworth; Matthew A Brown Journal: Nat Genet Date: 2013-06-09 Impact factor: 38.330