English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

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

Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy