Abstract
ABSTRACTBackgroundAmong individuals with high-riskAPOL1genotypes, the lifetime risk of developing kidney failure is ∼15%, indicating that other genetic variants or non-genetic modifiers likely contribute substantially to an individual patient’s risk of progressive kidney disease. Here we estimate the prevalence and distribution of molecularly diagnosed Mendelian kidney diseases among patients with high-riskAPOL1genotypes undergoing commercial genetic testing in the United States.MethodsWe analyzed clinical exome sequencing data from 15,181 individuals undergoing commercial genetic testing for Mendelian kidney disease in the United States from 2020-2021. We identified patients with high-riskAPOL1genotypes by the presence of G1/G1, G1/G2, or G2/G2 alleles. Patients carrying single riskAPOL1alleles were identified as G1/G0, G2/G0; the remainder of patients were G0/G0. We estimated the prevalence and distribution of molecularly diagnosed Mendelian kidney disease stratified byAPOL1genotype.ResultsOf 15,181 patients, 3119 had genetic testing results consistent with a molecular diagnosis of Mendelian kidney disease (20.5%). 1035 (6.8%) had high-riskAPOL1genotypes. The prevalence of molecularly diagnosed Mendelian kidney diseases was lower in individuals with high-riskAPOL1genotypes (9.2%; n=95/1035) compared to single riskAPOL1allele carriers (14.4%; n=243/1687) and those with G0/G0APOL1genotypes (22.3%; n=2781/12459). The distribution of molecularly diagnosed Mendelian kidney diseases was broadly similar among patients with and without high-riskAPOL1genotypes.ConclusionsAmong patients undergoing clinical genetic testing, we found a relatively high rate of molecularly diagnosed Mendelian kidney disease in patients with high-riskAPOL1genotypes. Mendelian kidney disease may contribute to wide variation in rates of progression observed among patients with high-riskAPOL1genotypes.
Publisher
Cold Spring Harbor Laboratory