Journal Articles

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

Publication Date

12-9-2021

Journal

Nature Communications

Abstract

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.

Keywords

Adult, Aged, CpG Islands, DNA Methylation, Female, Glomerular Filtration Rate, Humans, Interferon Regulatory Factors, Kidney, Kidney Function Tests, LIM Domain Proteins, Male, Membrane Proteins, Middle Aged, Renal Insufficiency, Chronic, Transcription Factors

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