Genome-wide association and functional follow-up reveals new Loci for kidney function
- Authors
- Pattaro, C., Köttgen, A., Teumer, A., Garnaas, M., Böger, C.A., Fuchsberger, C., Olden, M., Chen, M.H., Tin, A., Taliun, D., Li, M., Gao, X., Gorski, M., Yang, Q., Hundertmark, C., Foster, M.C., O'Seaghdha, C.M., Glazer, N., Isaacs, A., Liu, C.T., Smith, A.V., O'Connell, J.R., Struchalin, M., Tanaka, T., Li, G., Johnson, A.D., Gierman, H.J., Feitosa, M., Hwang, S.J., Atkinson, E.J., Lohman, K., Cornelis, M.C., Johansson, A., Tönjes, A., Dehghan, A., Chouraki, V., Holliday, E.G., Sorice, R., Kutalik, Z., Lehtimäki, T., Esko, T., Deshmukh, H., Ulivi, S., Chu, A.Y., Murgia, F., Trompet, S., Imboden, M., Kollerits, B., Pistis, G., Harris, T.B., Launer, L.J., Aspelund, T., Eiriksdottir, G., Mitchell, B.D., Boerwinkle, E., Schmidt, H., Cavalieri, M., Rao, M., Hu, F.B., Demirkan, A., Oostra, B.A., de Andrade, M., Turner, S.T., Ding, J., Andrews, J.S., Freedman, B.I., Koenig, W., Illig, T., Döring, A., Wichmann, H.E., Kolcic, I., Zemunik, T., Boban, M., Minelli, C., Wheeler, H.E., Igl, W., Zaboli, G., Wild, S.H., Wright, A.F., Campbell, H., Ellinghaus, D., Nöthlings, U., Jacobs, G., Biffar, R., Endlich, K., Ernst, F., Homuth, G., Kroemer, H.K., Nauck, M., Stracke, S., Völker, U., Völzke, H., Kovacs, P., Stumvoll, M., Mägi, R., Hofman, A., Uitterlinden, A.G., Rivadeneira, F., Aulchenko, Y.S., Polasek, O., Hastie, N., Vitart, V., Helmer, C., Wang, J.J., Ruggiero, D., Bergmann, S., Kähönen, M., Viikari, J., Nikopensius, T., Province, M., Ketkar, S., Colhoun, H., Doney, A., Robino, A., Giulianini, F., Krämer, B.K., Portas, L., Ford, I., Buckley, B.M., Adam, M., Thun, G.A., Paulweber, B., Haun, M., Sala, C., Metzger, M., Mitchell, P., Ciullo, M., Kim, S.K., Vollenweider, P., Raitakari, O., Metspalu, A., Palmer, C., Gasparini, P., Pirastu, M., Jukema, J.W., Probst-Hensch, N.M., Kronenberg, F., Toniolo, D., Gudnason, V., Shuldiner, A.R., Coresh, J., Schmidt, R., Ferrucci, L., Siscovick, D.S., van Duijn, C.M., Borecki, I., Kardia, S.L., Liu, Y., Curhan, G.C., Rudan, I., Gyllensten, U., Wilson, J.F., Franke, A., Pramstaller, P.P., Rettig, R., Prokopenko, I., Witteman, J.C., Hayward, C., Ridker, P., Parsa, A., Bochud, M., Heid, I.M., Goessling, W., Chasman, D.I., Kao, W.H., and Fox, C.S.
- ID
- ZDB-PUB-120409-12
- Date
- 2012
- Source
- PLoS Genetics 8(3): e1002584 (Journal)
- Registered Authors
- Garnaas, Maija, Goessling, Wolfram, Hastie, Nicholas D., Imboden, Medea
- Keywords
- Embryos, Genetic loci, Chronic kidney disease, Kidneys, Genome-wide association studies, Meta-analysis, Diabetes mellitus, Edema
- MeSH Terms
-
- Female
- Gene Knockdown Techniques
- Humans
- Male
- Aged
- Kidney Failure, Chronic/genetics*
- Kidney Failure, Chronic/pathology
- Animals
- Middle Aged
- DNA Helicases/genetics
- Genome-Wide Association Study*
- Follow-Up Studies
- Caspase 9/genetics
- Black or African American/genetics
- Glomerular Filtration Rate/genetics*
- Kidney/physiopathology*
- Phosphoric Diester Hydrolases/genetics
- White People/genetics
- DEAD-box RNA Helicases/genetics
- Zebrafish/genetics*
- Cyclin-Dependent Kinases/genetics
- PubMed
- 22479191 Full text @ PLoS Genet.
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.