Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
作者： Olga Gorlova , Jose-Ezequiel Martin , Blanca Rueda , Bobby PC Koeleman , Jun Ying
DOI: 10.1371/JOURNAL.PGEN.1002178
关键词:
摘要: The aim of this study was to determine, through a genome-wide association (GWAS), the genetic components contributing different clinical sub-phenotypes systemic sclerosis (SSc). We considered limited (lcSSc) and diffuse (dcSSc) cutaneous involvement, relationships with presence SSc-specific auto-antibodies, anti-centromere (ACA), anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients 5,171 healthy controls, were meta-analyzed looking for associations in selected subgroups. Eighteen polymorphisms further tested nine independent cohorts an additional 3,175 4,971 controls. Conditional analysis associated SNPs HLA region performed explore their antibody Overall showed that non-HLA polymorphism rs11642873 IRF8 gene be at level lcSSc (P = 2.32×10(-12), OR = 0.75). Also, rs12540874 GRB10 (P = 1.27 × 10(-6), OR = 1.15) rs11047102 SOX5 (P = 1.39×10(-7), OR = 1.36) suggestive ACA subgroups respectively. In region, we observed highly allelic combinations HLA-DQB1 locus (P = 1.79×10(-61), OR = 2.48), HLA-DPA1/B1 loci ATA (P = 4.57×10(-76), OR = 8.84), NOTCH4 P = 8.84×10(-21), OR = 0.55) (P = 1.14×10(-8), OR = 0.54). have identified three new genes (IRF8, GRB10, SOX5) auto-antibody Within HLA-DQB1, HLA-DPA1/B1, are likely confined specific auto-antibodies. These data emphasize differential subphenotypes SSc.
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