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Meta-analyses identify DNA methylation associated with kidney function and damage.

Nature communications

Authors: Pascal Schlosser, Adrienne Tin, Pamela R Matias-Garcia, Chris H L Thio, Roby Joehanes, Hongbo Liu, Antoine Weihs, Zhi Yu, Anselm Hoppmann, Franziska Grundner-Culemann, Josine L Min, Adebowale A Adeyemo, Charles Agyemang, Johan Ärnlöv, Nasir A 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, Marjo-Riitta Jarvelin, Sharon L R Kardia, Silva Kasela, Marcus E Kleber, Wolfgang Koenig, 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 A C Meeks, Lili Milani, Pashupati P Mishra, Matthias Nauck, Ana Navas-Acien, 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 R Stocker, Silvia Stringhini, Johan Sundström, Brenton R Swenson, Maria Tellez-Plaza, Joyce B J van Meurs, Jana V van Vliet-Ostaptchouk, Andrea Venema, Niek Verweij, Rosie M Walker, Matthias Wielscher, Juliane Winkelmann, Bruce H R Wolffenbuttel, Wei Zhao, Yinan Zheng, Marie Loh, Harold Snieder, Daniel Levy, Melanie Waldenberger, Katalin Susztak, Anna Köttgen, Alexander Teumer

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.

© 2021. The Author(s).

PMID: 34887417

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