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

Chronic kidney disease (CKD) is an important public health problem
with a genetic component. We performed genomewide 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.