Genetics of IgA nephrology: risks, mechanisms, and therapeutic targets

• Published in: Pediatric nephrology (Berlin, West) Vol. 39; no. 11; pp. 3157 - 3165
• Main Authors: Qu, Shu, Zhou, Xu-jie, Zhang, Hong
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.11.2024; Springer Nature B.V
• Subjects: Asian people; Biomarkers; Biopsy; Epidemiology; Ethnicity; Galactose; Genome-wide association studies; Genomes; Heritability; IgA nephropathy; Immunoglobulin A; Immunoglobulins; Kidney diseases; Medical treatment; Medicine; Medicine & Public Health; Molecular modelling; Nephrology; Pathogenesis; Pediatrics; Polygenic inheritance; Population genetics; Population studies; Review; Therapeutic targets; Urology; Glomerulonephritis; Immunoglobulin A nephropathy; Pathogenesis; Galactose-deficient IgA1; Therapeutic targets
• ISSN: 0931-041X; 1432-198X; 1432-198X
• DOI: 10.1007/s00467-024-06369-7

IgA nephropathy (IgAN) is a genetically complex multifactorial trait. Over the past decade, population-based genome-wide association studies (GWAS) have identified more than 30 IgAN risk loci, providing novel perspectives on both the epidemiology of the disease and its underlying molecular mechanisms. In addition, the association between IgAN and galactose-deficient IgA1 (Gd-IgA1) presented another avenue for genetic exploration due to the heritability of the elevated serum Gd-IgA1 levels. These endeavors also yielded and enabled refinement of polygenic risk scores, which may help identify specific groups of individuals at significantly increased risks, leading to stratifications of medical treatments. In this review, we aim to explore the existing evidence for genetic causation in IgAN. We summarize the state of genetic research in IgAN and how it has led to the reformulation of the new pathogenesis model and novel therapeutic targets. Graphical Abstract