Annals of the rheumatic diseases · 2016
A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14.
СтатьяМетаанализНазвание и аннотация: Перевод в очереди
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Costantino Félicie, Talpin Alice, Said-Nahal Roula, Leboime Ariane, Zinovieva Elena, Zelenika Diana, Gut Ivo, Charon Céline, Izac Brigitte, Weissman Michael, Chiocchia Gilles, Reveille John, Breban Maxime, Garchon Henri-Jean
Аннотация
OBJECTIVE: More than 40 loci have been associated with ankylosing spondylitis (AS), but less is known about genetic associations in spondyloarthritis (SpA) as a whole. We conducted a family-based genome-wide association study (GWAS) to identify new non-major histocompatibility complex (MHC) genetic factors associated with SpA.
METHODS: 906 subjects from 156 French multiplex families, including 438 with SpA, were genotyped using Affymetrix 250K microarrays. Association was tested with Unphased. The best-associated non-MHC single nucleotide polymorphisms (SNPs) were then genotyped in two independent familial cohorts (including 215 French and 294 North American patients with SpA, respectively) to replicate associations.
RESULTS: 43 non-MHC SNPs yielded an association signal with SpA in the discovery cohort (p<1×10-4). In the extension studies, association was replicated at a nominal p value of p<0.05 for 16 SNPs in the second cohort and for three SNPs in the third cohort. Combined analysis identified an association close to genome-wide significance between rs7761118, an intronic SNP of MAPK14, and SpA (p=3.5×10-7). Such association appeared to be independent of HLA-B27.
CONCLUSIONS: We report here for the first time a family-based GWAS study on SpA and identified an associated polymorphism near MAPK14. Further analyses are needed to better understand the functional basis of this genetic association.
METHODS: 906 subjects from 156 French multiplex families, including 438 with SpA, were genotyped using Affymetrix 250K microarrays. Association was tested with Unphased. The best-associated non-MHC single nucleotide polymorphisms (SNPs) were then genotyped in two independent familial cohorts (including 215 French and 294 North American patients with SpA, respectively) to replicate associations.
RESULTS: 43 non-MHC SNPs yielded an association signal with SpA in the discovery cohort (p<1×10-4). In the extension studies, association was replicated at a nominal p value of p<0.05 for 16 SNPs in the second cohort and for three SNPs in the third cohort. Combined analysis identified an association close to genome-wide significance between rs7761118, an intronic SNP of MAPK14, and SpA (p=3.5×10-7). Such association appeared to be independent of HLA-B27.
CONCLUSIONS: We report here for the first time a family-based GWAS study on SpA and identified an associated polymorphism near MAPK14. Further analyses are needed to better understand the functional basis of this genetic association.