Meta-analyses identify DNA methylation associated with kidney function and damage
Authors: Schlosser Pascal , Tin Adrienne , Matias-Garcia Pamela R. , Thio Chris H. L. , Joehanes Roby , Liu Hongbo , Weihs Antoine , Yu Zhi , Hoppmann Anselm , Grundner-Culemann Franziska , Min Josine L. , Adeyemo Adebowale A. , Agyemang Charles , Ärnlöv Johan , Aziz Nasir A. , Baccarelli Andrea , Bochud Murielle , Brenner Hermann , Breteler Monique M. B. , Carmeli Cristian , Chaker Layal , Chambers John C. , Cole Shelley A. , Coresh Josef , Corre Tanguy , Correa Adolfo , Cox Simon R. , de Klein Niek , Delgado Graciela E. , Domingo-Relloso Arce , Eckardt Kai-Uwe , Ekici Arif B. , Endlich Karlhans , Evans Kathryn L. , Floyd James S. , Fornage Myriam , Franke Lude , Fraszczyk Eliza , Gao Xu , Gào Xīn , Ghanbari Mohsen , Ghasemi Sahar , Gieger Christian , Greenland Philip , Grove Megan L. , Harris Sarah E. , Hemani Gibran , Henneman Peter , Herder Christian , Horvath Steve , Hou Lifang , Hurme Mikko A. , Hwang Shih-Jen , Jarvelin Marjo-Riitta , Kardia Sharon L. R. , Kasela Silva , Kleber Marcus E. , Koenig Wolfgang , Kooner Jaspal S. , Kramer Holly , Kronenberg Florian , Kühnel Brigitte , Lehtimäki Terho , Lind Lars , Liu Dan , Liu Yongmei , Lloyd-Jones Donald M. , Lohman Kurt , Lorkowski Stefan , Lu Ake T. , Marioni Riccardo E. , März Winfried , McCartney Daniel L. , Meeks Karlijn A. C. , Milani Lili , Mishra Pashupati P. , Nauck Matthias , Navas-Acien Ana , Nowak Christoph , Peters Annette , Prokisch Holger , Psaty Bruce M. , Raitakari Olli T. , Ratliff Scott M. , Reiner Alex P. , Rosas Sylvia E. , Schöttker Ben , Schwartz Joel , Sedaghat Sanaz , Smith Jennifer A. , Sotoodehnia Nona , Stocker Hannah R. , Stringhini Silvia , Sundström Johan , Swenson Brenton R. , Tellez-Plaza Maria , van Meurs Joyce B. J. , van Vliet-Ostaptchouk Jana V. , Venema Andrea , Verweij Niek , Walker Rosie M. , Wielscher Matthias , Winkelmann Juliane , Wolffenbuttel Bruce H. R. , Zhao Wei , Zheng Yinan ,   Estonian Biobank Research Team, Milani Lili ,   Genetics of DNA Methylation Consortium, Loh Marie , Snieder Harold , Levy Daniel , Waldenberger Melanie , Susztak Katalin , Köttgen Anna , Teumer Alexander 
Published: December 2021

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.