Genome-wide association and functional follow-up reveals new loci for kidney function

PLoS Genet. 2012;8(3):e1002584. doi: 10.1371/journal.pgen.1002584. Epub 2012 Mar 29.


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.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Aged
  • Animals
  • Black or African American / genetics
  • Caspase 9 / genetics
  • Cyclin-Dependent Kinases / genetics
  • DEAD-box RNA Helicases / genetics
  • DNA Helicases / genetics
  • DNA-Binding Proteins
  • Female
  • Follow-Up Studies
  • Gene Knockdown Techniques
  • Genome-Wide Association Study*
  • Glomerular Filtration Rate / genetics*
  • Humans
  • Kidney / physiopathology*
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / pathology
  • Male
  • Middle Aged
  • Phosphoric Diester Hydrolases / genetics
  • White People / genetics
  • Zebrafish / genetics*


  • DNA-Binding Proteins
  • CDK12 protein, human
  • Cyclin-Dependent Kinases
  • MPPED2 protein, human
  • Phosphoric Diester Hydrolases
  • CASP9 protein, human
  • Caspase 9
  • DDX1 protein, human
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • INO80 protein, human
  • DEAD-box RNA Helicases

Grant support