Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

Abstract

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near (MPPED2), (DDX1), (SLC47A1), (CDK12), (CASP9), and (INO80). Morpholino knockdown of (mpped2) and (casp9) in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.