A family-based genome-wide association study reveals an association of spondyloarthritis with MAPK14

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 −4 ). In the extension studies, association was replicated at a nominal p value of p 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.