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

Cristian Pattaro, Anna Köttgen, Alexander Teumer, Maija Garnaas, Carsten A Böger, Christian Fuchsberger, Matthias Olden, Ming-Huei Chen, Adrienne Tin, Daniel Taliun, Man Li, Xiaoyi Gao, Mathias Gorski, Qiong Yang, Claudia Hundertmark, Meredith C Foster, Conall M O'Seaghdha, Nicole Glazer, Aaron Isaacs, Ching-Ti LiuAlbert V Smith, Jeffrey R O'Connell, Maksim Struchalin, Toshiko Tanaka, Guo Li, Andrew D Johnson, Hinco J Gierman, Mary Feitosa, Shih-Jen Hwang, Elizabeth J Atkinson, Kurt Lohman, Marilyn C Cornelis, Åsa Johansson, Anke Tönjes, Abbas Dehghan, Vincent Chouraki, Elizabeth G Holliday, Rossella Sorice, Zoltan Kutalik, Terho Lehtimäki, Tõnu Esko, Harshal Deshmukh, Sheila Ulivi, Audrey Y Chu, Federico Murgia, Stella Trompet, Medea Imboden, Barbara Kollerits, Giorgio Pistis, Jie Jin Wang, CARDIoGRAM Consortium

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)e1002584
JournalPlos Genetics
Volume8
Issue number3
DOIs
Publication statusPublished - 2012
Externally publishedYes

Keywords

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

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