Investigation of systemic lupus erythematosus (SLE) with integrating transcriptomics and genome wide association information

Systemic lupus erythematous (SEL) is a heterogeneous, systemic autoimmune disorder which is defined by its autoantibody pattern. Transcriptomic data analysis has shown pathways and immune system responses associated with SLE. Eight up-regulated genes (SOCE, MMP9, CXCL8, JUN, IL1B, NFKBIA, TNF and FOS) have been examined with four interactions among different pathways. These genes are associated with SNPs which have been identified through two datasets from SLE genome-wide association studies (GWAS). In this investigation, the GWAS results were integrated with pathway analysis of transcriptomes and several genes were detected with known SLE-related variations (TYK2, C5, SH2B, IRF5, IL2RA, STAT4, FCGR2A, IL7R, LYN, HLA-DRB and TNFAIP3). Pathway-based analysis on the Wikipathway Human Collection allowed the identification of prioritized variants in the relevant pathways, such as thymic stromal lymphopoietin (TSLP) signaling pathway linked to LYN, IL7R, STAT4 and rs7574865. Analysis of existing transcriptomes and GWAS data identified eight up-regulated candidate genes with more than four relationships among the different pathways associated with SNPs to pinpoint the relevant loci linked to SLE. The results of this investigation have expanded the number of candidate genes related to SLE and have highlighted possible pathways and GWAS-based methods for gene detection. Identification of the fundamental genes would assist in revealing the mechanisms responsible for SLE. •Understand the functions of Systemic Lupus Erythematosus (SLE)•Identified 8up-regulated candidate genes with using GWAS and transcriptomics analysis•Finding potential of pathways and GWAS- based approaches in gene discovery for SLE•Identification of the causal genes to elucidate mechanisms responsible for SLE disease