Publication

Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Teumer, A., Li, Y., Ghasemi, S., Prins, B. P., Wuttke, M., Hermle, T., Giri, A., Sieber, K. B., Qiu, C., Kirsten, H., Tin, A., Chu, A. Y., Bansal, N., Feitosa, M. F., Wang, L., Chai, J-F., Cocca, M., Fuchsberger, C., Gorski, M., Hoppmann, A., Horn, K., Li, M., Marten, J., Noce, D., Nutile, T., Sedaghat, S., Sveinbjornsson, G., Tayo, B. O., Van der Most, P. J., Xu, Y., Yu, Z., Gerstner, L., Arnlov, J., Bakker, S. J. L., Baptista, D., Biggs, M. L., Boerwinkle, E., Brenner, H., Burkhardt, R., Carroll, R. J., Chee, M-L., Chee, M-L., Chen, M., Cheng, C-Y., Cook, J. P., Coresh, J., Corre, T., Danesh, J., de Borst, M. H., De Grandi, A., de Mutsert, R., de Vries, A. P. J., Degenhardt, F., Dittrich, K., Divers, J., Eckardt, K-U., Ehret, G., Endlich, K., Felix, J. F., Franco, O. H., Franke, A., Freedman, B. I., Freitag-Wolf, S., Gansevoort, R. T., Giedraitis, V., Gogele, M., Grundner-Culemann, F., Gudbjartsson, D. F., Gudnason, V., Hamet, P., Harris, T. B., Hicks, A. A., Holm, H., Foo, V. H. X., Hwang, S-J., Ikram, M. A., Ingelsson, E., Jaddoe, V. W. V., Jakobsdottir, J., Josyula, N. S., Jung, B., Kahonen, M., Khor, C-C., Kiess, W., Koenig, W., Koerner, A., Kovacs, P., Kramer, H., Kraemer, B. K., Kronenberg, F., Lange, L. A., Langefeld, C. D., Lee, J. J-M., Lehtimaki, T., Lieb, W., Lim, S-C., Lind, L., Lindgren, C. M., Liu, J., Loeffler, M., Lyytikainen, L-P., Mahajan, A., Maranville, J. C., Mascalzoni, D., McMullen, B., Meisinger, C., Meitinger, T., Miliku, K., Mook-Kanamori, D. O., Mueller-Nurasyid, M., Mychaleckyj, J. C., Nauck, M., Nikus, K., Ning, B., Noordam, R., Connell, J. O., Olafsson, I., Palmer, N. D., Peters, A., Podgornaia, A. I., Ponte, B., Poulain, T., Pramstaller, P. P., Rabelink, T. J., Raffield, L. M., Reilly, D. F., Rettig, R., Rheinberger, M., Rice, K. M., Rivadeneira, F., Runz, H., Ryan, K. A., Sabanayagam, C., Saum, K-U., Schoettker, B., Shaffer, C. M., Shi, Y., Smith, A. V., Strauch, K., Stumvoll, M., Sun, B. B., Szymczak, S., Tai, E-S., Tan, N. Y. Q., Taylor, K. D., Teren, A., Tham, Y-C., Thiery, J., Thio, C. H. L., Thomsen, H., Thorsteinsdottir, U., Tonjes, A., Tremblay, J., Uitterlinden, A. G., Van der Harst, P., Verweij, N., Vogelezang, S., Voelker, U., Waldenberger, M., Wang, C., Wilson, O. D., Wong, C., Wong, T-Y., Yang, Q., Yasuda, M., Akilesh, S., Bochud, M., Boeger, C. A., Devuyst, O., Edwards, T. L., Ho, K., Morris, A. P., Parsa, A., Pendergrass, S. A., Psaty, B. M., Rotter, J. I., Stefansson, K., Wilson, J. G., Susztak, K., Snieder, H., Heid, I. M., Scholz, M., Butterworth, A. S., Hung, A. M., Pattaro, C. & Koettgen, A., 11-Sep-2019, In : Nature Communications. 10, 1, p. 4130 19 p., 4130.

Research output: Contribution to journalArticleAcademicpeer-review

  • Alexander Teumer
  • Yong Li
  • Sahar Ghasemi
  • Bram P. Prins
  • Matthias Wuttke
  • Tobias Hermle
  • Ayush Giri
  • Karsten B. Sieber
  • Chengxiang Qiu
  • Holger Kirsten
  • Adrienne Tin
  • Audrey Y. Chu
  • Nisha Bansal
  • Mary F. Feitosa
  • Lihua Wang
  • Jin-Fang Chai
  • Massimiliano Cocca
  • Christian Fuchsberger
  • Mathias Gorski
  • Anselm Hoppmann
  • Katrin Horn
  • Man Li
  • Jonathan Marten
  • Damia Noce
  • Teresa Nutile
  • Sanaz Sedaghat
  • Gardar Sveinbjornsson
  • Bamidele O. Tayo
  • Peter J. Van der Most
  • Yizhe Xu
  • Zhi Yu
  • Lea Gerstner
  • Johan Arnlov
  • Stephan J. L. Bakker
  • Daniela Baptista
  • Mary L. Biggs
  • Eric Boerwinkle
  • Hermann Brenner
  • Ralph Burkhardt
  • Robert J. Carroll
  • Miao-Li Chee
  • Miao-Ling Chee
  • Mengmeng Chen
  • Ching-Yu Cheng
  • James P. Cook
  • Josef Coresh
  • Tanguy Corre
  • John Danesh
  • Martin H. de Borst
  • Alessandro De Grandi
  • Renee de Mutsert
  • Aiko P. J. de Vries
  • Frauke Degenhardt
  • Katalin Dittrich
  • Jasmin Divers
  • Kai-Uwe Eckardt
  • Georg Ehret
  • Karlhans Endlich
  • Janine F. Felix
  • Oscar H. Franco
  • Andre Franke
  • Barry I. Freedman
  • Sandra Freitag-Wolf
  • Ron T. Gansevoort
  • Vilmantas Giedraitis
  • Martin Gogele
  • Franziska Grundner-Culemann
  • Daniel F. Gudbjartsson
  • Vilmundur Gudnason
  • Pavel Hamet
  • Tamara B. Harris
  • Andrew A. Hicks
  • Hilma Holm
  • Valencia Hui Xian Foo
  • Shih-Jen Hwang
  • M. Arfan Ikram
  • Erik Ingelsson
  • Vincent W. V. Jaddoe
  • Johanna Jakobsdottir
  • Navya Shilpa Josyula
  • Bettina Jung
  • Mika Kahonen
  • Chiea-Chuen Khor
  • Wieland Kiess
  • Wolfgang Koenig
  • Antje Koerner
  • Peter Kovacs
  • Holly Kramer
  • Bernhard K. Kraemer
  • Florian Kronenberg
  • Leslie A. Lange
  • Carl D. Langefeld
  • Jeannette Jen-Mai Lee
  • Terho Lehtimaki
  • Wolfgang Lieb
  • Su-Chi Lim
  • Lars Lind
  • Cecilia M. Lindgren
  • Jianjun Liu
  • Markus Loeffler
  • Leo-Pekka Lyytikainen
  • Anubha Mahajan
  • Joseph C. Maranville
  • Deborah Mascalzoni
  • Barbara McMullen
  • Christa Meisinger
  • Thomas Meitinger
  • Kozeta Miliku
  • Dennis O. Mook-Kanamori
  • Martina Mueller-Nurasyid
  • Josyf C. Mychaleckyj
  • Matthias Nauck
  • Kjell Nikus
  • Boting Ning
  • Raymond Noordam
  • Jeffrey O' Connell
  • Isleifur Olafsson
  • Nicholette D. Palmer
  • Annette Peters
  • Anna I. Podgornaia
  • Belen Ponte
  • Tanja Poulain
  • Peter P. Pramstaller
  • Ton J. Rabelink
  • Laura M. Raffield
  • Dermot F. Reilly
  • Rainer Rettig
  • Myriam Rheinberger
  • Kenneth M. Rice
  • Fernando Rivadeneira
  • Heiko Runz
  • Kathleen A. Ryan
  • Charumathi Sabanayagam
  • Kai-Uwe Saum
  • Ben Schoettker
  • Christian M. Shaffer
  • Yuan Shi
  • Albert V. Smith
  • Konstantin Strauch
  • Michael Stumvoll
  • Benjamin B. Sun
  • Silke Szymczak
  • E-Shyong Tai
  • Nicholas Y. Q. Tan
  • Kent D. Taylor
  • Andrej Teren
  • Yih-Chung Tham
  • Joachim Thiery
  • Chris H. L. Thio
  • Hauke Thomsen
  • Unnur Thorsteinsdottir
  • Anke Tonjes
  • Johanne Tremblay
  • Andre G. Uitterlinden
  • Pim Van der Harst
  • Niek Verweij
  • Suzanne Vogelezang
  • Uwe Voelker
  • Melanie Waldenberger
  • Chaolong Wang
  • Otis D. Wilson
  • Charlene Wong
  • Tien-Yin Wong
  • Qiong Yang
  • Masayuki Yasuda
  • Shreeram Akilesh
  • Murielle Bochud
  • Carsten A. Boeger
  • Olivier Devuyst
  • Todd L. Edwards
  • Kevin Ho
  • Andrew P. Morris
  • Afshin Parsa
  • Sarah A. Pendergrass
  • Bruce M. Psaty
  • Jerome I. Rotter
  • Kari Stefansson
  • James G. Wilson
  • Katalin Susztak
  • Harold Snieder
  • Iris M. Heid
  • Markus Scholz
  • Adam S. Butterworth
  • Adriana M. Hung
  • Cristian Pattaro
  • Anna Koettgen

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n =192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

Original languageEnglish
Article number4130
Pages (from-to)4130
Number of pages19
JournalNature Communications
Volume10
Issue number1
Publication statusPublished - 11-Sep-2019

    Keywords

  • GLOMERULAR-FILTRATION-RATE, LD SCORE REGRESSION, KIDNEY-DISEASE, CARDIOVASCULAR EVENTS, COLLABORATIVE METAANALYSIS, BLOOD-PRESSURE, EXCRETION RATE, TRANS-EQTLS, HERITABILITY, RISK

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