UBD modifies APOL1 -induced kidney disease risk

Significance Two common variants in the APOL1 gene explain most of the high rate of kidney disease in people of recent African ancestry. However, not all APOL1 high-risk individuals develop kidney disease. Here we identified the UBD locus as a genetic modifier of APOL1 kidney disease using admixture mapping. Focal segmental glomerulosclerosis patients have significantly increased African ancestry at the UBD locus, which associates with lower UBD gene expression. Using a cell-based system, we show that UBD and APOL1 interact functionally and that higher levels of UBD expression mitigate APOL1 -mediated cell death. These findings are important for understanding the genetic and functional modifiers of the human APOL1 -associated phenotype and the biological pathways relevant to APOL1 -associated cell damage.