Rare Kidney Function, Disease Variants Found With Imputation-Based Strategy

In Nature Communications, a team from the University of Freiburg and other centers in Germany, Italy, and the US reports on rare kidney function- and kidney disease-associated variants found through an imputation-informed exome-wide association study. Starting with exome sequence data for nearly 166,900 individuals, the researchers used imputation to search for ties between five kidney function traits and almost 7.6 million variants 408,511 UK Biobank participants of European ancestry, evaluating their results in relation to kidney disease reports from corresponding clinical record data and growing UK Biobank exome sequence data. In the process, the authors flagged 158 rare variants and more than 100 genes linked to kidney function, including splice or frameshift variants not found in the past. "This cost-efficient approach boosts statistical power to detect and characterize both known and novel disease susceptibility variants and genes, can be generalized to larger future studies, and generates a comprehensive resource to direct experimental and clinical studies of kidney disease," they write, noting that the current study "revealed genetic determinant of kidney function and will help to direct future functional and clinical studies."