GIGA-kids: Genomics of IgA-Related Diseases in Kids

IgA nephropathy (IgAN) represents the leading cause of kidney failure among young adults, and the most frequent form of primary glomerulonephritis worldwide. Our recent studies define IgAN as an autoimmune trait of complex architecture with a strong genetic determination. We have recently discovered several common genetic variants predisposing to IgAN in adults through a large-scale genome-wide association study (GWAS). We also discovered a strong relationship between the load of GWAS-identified risk alleles and the age of disease onset, suggesting that pediatric patients with IgAN may carry a significantly higher burden of genetic risk factors. Accordingly, we would like to extend our genetic investigations to children affected by IgAN and Henoch- Schönlein purpura (HSP) without or with nephritis (HSPN), two IgA-related syndromes with skin manifestations. This proposal aims at (1) validation of adult genetic and biochemical disease predictors in pediatric patients with IgAN and HSP with and without nephritis, and (2) discovery of new genetic and biomarker predictors of disease based on pediatric cohorts.