Genetics of autoimmune diseases: perspectives from genome-wide association studies

Abstract

Genome-wide association studies (GWASs) for autoimmune diseases (ADs) have identified many risk loci and have provided insights into the etiology of each disease. Some of these loci, such asPTPN22,IL23RandSTAT4, are shared among different ADs, and the combination of risk loci may determine an individual's susceptibility for a disease. The majority of GWAS loci are expression quantitative trait loci (eQTLs), where disease-causing variants regulate expression of neighboring (or sometimes distant) genes. Because the eQTL effects are often cell type-specific, the incorporation of epigenetic data from disease-related cell types and tissues is expected to refine the identification of causal variants. The cumulative eQTL effects in multiple genes may influence the activity or fate of immune cells, which in turn may affect the function of the immune system in individuals. In this paper, I review the etiology of ADs by focusing on important immune cells (Th1 cells, Th17 cells and regulatory T cells), important pathways (antigen-receptor signaling and type I interferon signaling) and relevant genes identified in GWASs.

Keywords: autoimmune disease; expression quantitative trait locus; genome-wide association study.