IRF4- The new common Systemic Sclerosis (SSc)- Rheumatoid Arthritis (RA) loci
Many clinical and immunological features are shared by Systemic sclerosis (SSc) and Rheumatoid arthritis (RA) which are the types of autoimmune diseases. Any shared SSc-RA loci have been identified independently till now. Here, by using the inter-disease meta-GWAS strategy we searched upon new SSc-RA loci.
Strategy implementation of allowing the identification of loci with same-direction and opposing-direction allelic effects by integrating GWAS datasets lead to promising results. The independent SSc and RA case-control cohorts also depicted the top single-nucleotide polymorphisms (SNPs). Hence, permitting to expand the sample size of 8,830 SSc patients, with 16,870 RA patients and 43,393 controls.
Various loci with nominal association signals (P-value <5 X 10-6) and confirmation of association on disease-specific GWAS scan was a result of the meta-analysis of the GWAS datasets. Different genomic regions were delineated which were otherwise not reported as shared loci. Identification of novel IRF4 as a shared risk factor for these two diseases (Pcombined = 3.29 x 10-12) was a resultant of alleged new SSc-RA loci. Also, the type I interferon and the interleukin 12 signaling pathways were proved as key common etiopathogenic factors on the analysis of biological relevance. GWAS meta-analysis was significant in putting forward the identification of common risk loci.