Lupus susceptibility genes

Abstract

Abstract Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with established genetic susceptibility. Genetic studies have revealed that SLE is largely a complex genetic disease influenced by the cumulative effect of multiple genetic variants, most of which are nonprotein coding, dispersed across the genome. Research has successfully identified more than 120 risk loci, defined mainly by haplotypes (a set of variants that are coinherited), that are associated with increased SLE susceptibility. Current efforts use publicly available bioinformatics data, fine-mapping and/or dense imputation, and molecular studies to identify the functional variants that drive the haplotype association and pathologic effect. In this chapter, we emphasize the complex genetic heritability of SLE by highlighting several risk associations from the current literature that demonstrate the complexity and recent advances in our understanding of how non-HLA SLE-susceptibility loci contribute to disease pathology.