Genes and Genetics in Human Systemic Lupus Erythematosus

The complex etiology of systemic lupus erythematosus (SLE) could be attributed to a combination of genetic predispositions, epigenetic changes, and environmental exposures. The genome-wide association study (GWAS) that screens hundreds of thousands of single nucleotide polymorphisms across the genome based on a hypothesis-free approach has accelerated discovery of genetic variants predisposing individuals to SLE. After the initial GWAS discovery, subsequent large-scale replication studies and meta-analyses have identified and confirmed over 50 SLE-risk loci that most are shared in multiple ancestries. We review recent progress toward identifying causative variants at the SLE-risk loci, highlighting genes with functions in innate and adaptive immune responses that contribute to disease susceptibility and specific manifestations or end organ damage in SLE. These findings have enhanced our understanding of SLE pathogenesis to the molecular level and will guide the development of new therapeutic interventions in the near future.