An Update on the Genetics of IgA Nephropathy

Abstract

Immunoglobulin A (IgA) nephropathy (IgAN), the most common form of glomerulonephritis, is one of the leading causes of end-stage kidney disease (ESKD). It is widely believed that genetic factors play a significant role in the development of IgAN. Previous studies of IgAN have provided important insights to unravel the genetic architecture of IgAN and its potential pathogenic mechanisms. The genome-wide association studies (GWASs) together have identified over 30 risk loci for IgAN, which emphasizes the importance of IgA production and regulation in the pathogenesis of IgAN. Follow-up fine-mapping studies help to elucidate the candidate causal variant and the potential pathogenic molecular pathway and provide new potential therapeutic targets. With the rapid development of next-generation sequencing technologies, linkage studies based on whole-genome sequencing (WGS)/whole-exome sequencing (WES) also identify rare variants associated with IgAN, accounting for some of the missing heritability. The complexity of pathogenesis and phenotypic variability may be better understood by integrating genetics, epigenetics, and environment. We have compiled a review summarizing the latest advancements in genetic studies on IgAN. We similarly summarized relevant studies examining the involvement of epigenetics in the pathogenesis of IgAN. Future directions and challenges in this field are also proposed.