A catalog of genetic loci associated with kidney function from analyses of a million individuals

Wuttke, M. et al. (2019) A catalog of genetic loci associated with kidney function from analyses of a million individuals. Nature Genetics, 51(6), pp. 957-972. (doi: 10.1038/s41588-019-0407-x) (PMID:31152163) (PMCID:PMC6698888)

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Abstract

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Padmanabhan, Professor Sandosh
Authors: Wuttke, M., Li, Y., Li, M., Sieber, K. B., Feitosa, M. F., Gorski, M., Tin, A., Wang, L., Chu, A. Y., Hoppmann, A., Kirsten, H., Giri, A., Chai, J.-F., Sveinbjornsson, G., Tayo, B. O., Nutile, T., Fuchsberger, C., Marten, J., Cocca, M., Ghasemi, S., Xu, Y., Horn, K., Noce, D., van der Most, P. J., Sedaghat, S., Yu, Z., Akiyama, M., Afaq, S., Ahluwalia, T. S., Almgren, P., Amin, N., Ärnlöv, J., Bakker, S. J. L., Bansal, N., Baptista, D., Bergmann, S., Biggs, M. L., Biino, G., Boehnke, M., Boerwinkle, E., Boissel, M., Bottinger, E. P., Boutin, T. S., Brenner, H., Brumat, M., Burkhardt, R., Butterworth, A. S., Campana, E., Campbell, A., Campbell, H., Canouil, M., Carroll, R. J., Catamo, E., Chambers, J. C., Chee, M.-L., Chee, M.-L., Chen, X., Cheng, C.-Y., Cheng, Y., Christensen, K., Cifkova, R., Ciullo, M., Concas, M. P., Cook, J. P., Coresh, J., Corre, T., Sala, C. F., Cusi, D., Danesh, J., Daw, E. W., de Borst, M. H., De Grandi, A., de Mutsert, R., de Vries, A. P. J., Degenhardt, F., Delgado, G., Demirkan, A., Di Angelantonio, E., Dittrich, K., Divers, J., Dorajoo, R., Eckardt, K.-U., Ehret, G., Elliott, P., Endlich, K., Evans, M. K., Felix, J. F., Foo, V. H. X., Franco, O. H., Franke, A., Freedman, B. I., Freitag-Wolf, S., Friedlander, Y., Froguel, P., Gansevoort, R. T., Gao, H., Gasparini, P., Gaziano, J. M., Giedraitis, V., Gieger, C., Girotto, G., Giulianini, F., Gögele, M., Gordon, S. D., Gudbjartsson, D. F., Gudnason, V., Haller, T., Hamet, P., Harris, T. B., Hartman, C. A., Hayward, C., Hellwege, J. N., Heng, C.-K., Hicks, A. A., Hofer, E., Huang, W., Hutri-Kähönen, N., Hwang, S.-J., Ikram, M. A., Indridason, O. S., Ingelsson, E., Ising, M., Jaddoe, V. W. V., Jakobsdottir, J., Jonas, J. B., Joshi, P. K., Josyula, N. S., Jung, B., Kähönen, M., Kamatani, Y., Kammerer, C. M., Kanai, M., Kastarinen, M., Kerr, S. M., Khor, C.-C., Kiess, W., Kleber, M. E., Koenig, W., Kooner, J. S., Körner, A., Kovacs, P., Kraja, A. T., Krajcoviechova, A., Kramer, H., Krämer, B. K., Kronenberg, F., Kubo, M., Kühnel, B., Kuokkanen, M., Kuusisto, J., La Bianca, M., Laakso, M., Lange, L. A., Langefeld, C. D., Lee, J. J.-M., Lehne, B., Lehtimäki, T., Lieb, W., Lim, S.-C., Lind, L., Lindgren, C. M., Liu, J., Liu, J., Loeffler, M., Loos, R. J. F., Lucae, S., Lukas, M. A., Lyytikäinen, L.-P., Mägi, R., Magnusson, P. K. E., Mahajan, A., Martin, N. G., Martins, J., März, W., Mascalzoni, D., Matsuda, K., Meisinger, C., Meitinger, T., Melander, O., Metspalu, A., Mikaelsdottir, E. K., Milaneschi, Y., Miliku, K., Mishra, P. P., Mohlke, K. L., Mononen, N., Montgomery, G. W., Mook-Kanamori, D. O., Mychaleckyj, J. C., Nadkarni, G. N., Nalls, M. A., Nauck, M., Nikus, K., Ning, B., Nolte, I. M., Noordam, R., O'Connell, J., O'Donoghue, M. L., Olafsson, I., Oldehinkel, A. J., Orho-Melander, M., Ouwehand, W. H., Padmanabhan, S., Palmer, N. D., Palsson, R., Penninx, B. W. J. H., Perls, T., Perola, M., Pirastu, M., Pirastu, N., Pistis, G., Podgornaia, A. I., Polasek, O., Ponte, B., Porteous, D. J., Poulain, T., Pramstaller, P. P., Preuss, M. H., Prins, B. P., Province, M. A., Rabelink, T. J., Raffield, L. M., Raitakari, O. T., Reilly, D. F., Rettig, R., Rheinberger, M., Rice, K. M., Ridker, P. M., Rivadeneira, F., Rizzi, F., Roberts, D. J., Robino, A., Rossing, P., Rudan, I., Rueedi, R., Ruggiero, D., Ryan, K. A., Saba, Y., Sabanayagam, C., Salomaa, V., Salvi, E., Saum, K.-U., Schmidt, H., Schmidt, R., Schöttker, B., Schulz, C.-A., Schupf, N., Shaffer, C. M., Shi, Y., Smith, A. V., Smith, B. H., Soranzo, N., Spracklen, C. N., Strauch, K., Stringham, H. M., Stumvoll, M., Svensson, P. O., Szymczak, S., Tai, E.-S., Tajuddin, S. M., Tan, N. Y. Q., Taylor, K. D., Teren, A., Tham, Y.-C., Thiery, J., Thio, C. H. L., Thomsen, H., Thorleifsson, G., Toniolo, D., Tönjes, A., Tremblay, J., Tzoulaki, I., Uitterlinden, A. G., Vaccargiu, S., van Dam, R. M., van der Harst, P., van Duijn, C. M., Velez Edward, D. R., Verweij, N., Vogelezang, S., Völker, U., Vollenweider, P., Waeber, G., Waldenberger, M., Wallentin, L., Wang, Y. X., Wang, C., Waterworth, D. M., Bin Wei, W., White, H., Whitfield, J. B., Wild, S. H., Wilson, J. F., Wojczynski, M. K., Wong, C., Wong, T.-Y., Xu, L., Yang, Q., Yasuda, M., Yerges-Armstrong, L. M., Zhang, W., Zonderman, A. B., Rotter, J. I., Bochud, M., Psaty, B. M., Vitart, V., Wilson, J. G., Dehghan, A., Parsa, A., Chasman, D. I., Ho, K., Morris, A. P., Devuyst, O., Akilesh, S., Pendergrass, S. A., Sim, X., Böger, C. A., Okada, Y., Edwards, T. L., Snieder, H., Stefansson, K., Hung, A. M., Heid, I. M., Scholz, M., Teumer, A., Köttgen, A., and Pattaro, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cardiovascular and Medical Sciences
Journal Name:Nature Genetics
Publisher:Nature Publishing Group
ISSN:1061-4036
ISSN (Online):1546-1718
Published Online:31 May 2019
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in Nature Genetics 51(6):957-972
Publisher Policy:Reproduced in accordance with the copyright policy of the publisher

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