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

Gibson, G. et al. (2012) Genome-wide association and functional follow-up reveals new loci for kidney function. PLoS Genetics, 8(3), e1002584. (doi: 10.1371/journal.pgen.1002584)

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.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Ford, Professor Ian
• Authors: Gibson, G., 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, Å., 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.R., Liu, Y., Curhan, G.C., Rudan, I., Gyllensten, U., Wilson, J.F., Franke, A., Pramstaller, P.P., Rettig, R., Prokopenko, I., Witteman, J.C.M., Hayward, C., Ridker, P., Parsa, A., Bochud, M., Heid, I.M., Goessling, W., Chasman, D.I., Kao, W.H.L., and Fox, C.S.
• Subjects: R Medicine > R Medicine (General)
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre
• Journal Name: PLoS Genetics
• Publisher: Public Library of Science
• ISSN: 1553-7390
• ISSN (Online): 1553-7404
• Published Online: 29 March 2012
• Copyright Holders: Copyright © 2012 The Authors
• First Published: First published in PLoS Genetics 8(3):e1002584
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher