Archive | 2021
Genes and genetics in human SLE
Abstract
Abstract It is generally agreed that disease features of systemic lupus erythematosus (SLE) manifest in genetically predisposed individuals after encountering environmental triggers. Genome wide association studies provide an unbiased approach to screening hundreds of thousands of single nucleotide polymorphisms and have enhanced the discovery of genetic risk loci associated with SLE. Further advancements in the field (large-scale replication studies, meta-analysis, next generation sequencing, fine mapping of disease characteristics, and functional studies) have led a rapid increase in the discovery of SLE risk variants, approaching 150 loci identified. Although functions of a number of identified loci remain unknown, most risk gene products participate in various aspects of the immune system, including the clearance of immune complexes, type I interferon and NFkB pathways, B and T cell signaling, and transcriptional regulation, which are highlighted herein. Updated progress in lupus genetics, the identification of new causal variants, the discovery of novel pathways and regulatory mechanisms, and advances in utilizing SLE-risk loci to predict disease susceptibility and therapeutic strategies are reviewed. Here we emphasize the progress made in the last few years that has greatly enhanced our understanding of SLE pathogenesis, which will serve to guide the development of novel therapies to treat the disease.