A review of genetic risk in systemic lupus erythematosus

IntroductionSystemic Lupus Erythematosus (SLE) is a complex multisystem autoimmune disease with a wide range of signs and symptoms in affected individuals. The utilization of genome-wide association study (GWAS) technology has led to an explosion in the number of genetic risk factors mapped for autoimmune diseases, including SLE.Areas coveredIn this review, we summarize the more recent genetic risk loci mapped in SLE, which bring the total number of loci mapped to approximately 200. We review prioritization analyses of the associated variants and experimental validation of the putative causal variants. This includes the implementation of new bioinformatic techniques to align genomic and functional data and the use of transcriptomics with single-cell RNA-sequencing, CRISPR genome editing, and Massive Parallel Reporter Assays to analyze non-coding regulatory genetics.Expert opinionDespite progress in identifying more genetic risk loci and variant-gene pairs for SLE, understanding its pathogenesis and applying findings clinically remains challenging. The polygenic risk score (PRS) has been used as an application of SLE genetics, but with limited performance in non-EUR populations. In the next few years, advancements in proteomics, post-translational modification estimation, and whole-genome sequencing will enhance disease understanding.