ZFIN ID: ZDB-PUB-120409-12
Genome-wide association and functional follow-up reveals new Loci for kidney function
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.
Date:
2012
Source:
PLoS Genetics 8(3):
e1002584 (Journal)
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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:
African Americans/genetics
Aged
Animals
Caspase 9/genetics
Cyclin-Dependent Kinases/genetics
DEAD-box RNA Helicases/genetics
DNA Helicases/genetics
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*
Kidney Failure, Chronic/pathology
Male
Middle Aged
Phosphoric Diester Hydrolases/genetics
Zebrafish/genetics*
PubMed:
22479191
Full text @ PLoS Genet.
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.
