The Identification of Significant Genes Related to Systemic Lupus Erythematosus through the Integration of the Results of a Transcriptome-Wide Association Study and an mRNA Expression Profile Analysis

Abstract Background Systemic lupus erythematosus (SLE) is a polygenic autoimmune connective tissue disease in which heritable components play an essential role in the pathogenesis. However, the correlation between genetic variants and pathological changes in SLE is still unclear, and it is difficult to provide insights for the early diagnosis and treatment of SLE. Methods We conducted a transcriptome-wide association study (TWAS) of SLE by integrating a genome−wide association study (GWAS) summary dataset of SLE (538 diagnosed patients and 213,145 controls derived from the FinnGen consortium). To verify the results of the TWAS analysis, the significant genes were further compared with the mRNA expression profiles of SLE to screen for common genes. Finally, significant genes were analyzed using functional enrichment and annotation analysis in Metascape to examine SLE-related gene sets. Results The TWAS identified 30 genes with PTWAS−adjusted values < 1.33×10− 6 (0.05/37665 = 1.33×10− 6), including HCP5 (PTWAS =8.74×10− 15) and APOM (PTWAS = 4.57×10− 12). Four common genes were identified through the comparison of the TWAS results with the differentially expressed genes (DEGs) of SLE, including APOM (PTWAS = 4.57×10− 12, PDEG = 3.31×10− 02) and C2 (PTWAS = 8.04×10− 11, PDEG = 1.54×10− 02). Moreover, 36 terms were detected for the enrichment results of the TWAS, including antigen processing and presentation (logP value = -4.1938). By integrating the pathway and process enrichment analysis results of DEGs, 17 terms were identified, including allograft rejection (logP value = -7.5738). Conclusion The study identified a group of SLE-related genes and pathways, and the findings provide novel insights for the early diagnosis and intervention of SLE.