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Get Free AccessAbstract Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1 , PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1 , LDB2 , CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.
Pascal Schlosser, Adrienne Tin, Pamela R. Matías‐García, Chris H. L. Thio, Roby Joehanes, Hongbo Liu, Antoine Weihs, Zhi Yu, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L. Min, Adebowale Adeyemo, Charles Agyemang, Johan Ärnlöv, N. Ahmad Aziz, Andrea Baccarelli, Murielle Bochud, Hermann Brenner, Monique M.B. Breteler, Cristian Carmeli, Layal Chaker, John C. Chambers, Shelley A. Cole, Josef Coresh, Tanguy Corre, Adolfo Correa, Simon R. Cox, Niek de Klein, Graciela E. Delgado, Arce Domingo‐Relloso, Kai‐Uwe Eckardt, Arif B. Ekici, Karlhans Endlich, Kathryn L. Evans, James S. Floyd, Myriam Fornage, Lude Franke, Eliza Fraszczyk, Xu Gao, Xīn Gào, Mohsen Ghanbari, Sahar Ghasemi, Christian Gieger, Philip Greenland, Megan L. Grove, Sarah E. Harris, Gibran Hemani, Peter Henneman, Christian Herder, Steve Horvath, Lifang Hou, Mikko A. Hurme, Shih‐Jen Hwang, Paul M Ridker, Sharon L. R. Kardia, Silva Kasela, Marcus E. Kleber, Wolfgang Köenig, Jaspal S. Kooner, Holly Kramer, Florian Kronenberg, Brigitte Kühnel, Terho Lehtimäki, Lars Lind, Dan Liu, Yongmei Liu, Donald M. Lloyd‐Jones, Kurt Lohman, Stefan Lorkowski, Ake T. Lu, Riccardo E. Marioni, Winfried März, Daniel L. McCartney, Karlijn Meeks, Lili Milani, Pashupati P. Mishra, Matthias Nauck, Ana Navas‐Acién, Christoph Nowak, Annette Peters, Holger Prokisch, Bruce M. Psaty, Olli T. Raitakari, Scott M. Ratliff, Alex P. Reiner, Sylvia E. Rosas, Ben Schöttker, Joel Schwartz, Sanaz Sedaghat, Jennifer A. Smith, Nona Sotoodehnia, Hannah Stocker, Silvia Stringhini, Johan Sundström, Brenton R. Swenson, María Téllez-Plaza, Joyce B. J. van Meurs, Jana V. van Vliet‐Ostaptchouk, Andrea Venema, Niek Verweij (2021). Meta-analyses identify DNA methylation associated with kidney function and damage. , 12(1), DOI: https://doi.org/10.1038/s41467-021-27234-3.
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Type
Article
Year
2021
Authors
100
Datasets
0
Total Files
0
Language
en
DOI
https://doi.org/10.1038/s41467-021-27234-3
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