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Schlosser, P.* ; Tin, A.* ; Matias-Garcia, P.R. ; Thio, C.H.L.* ; Joehanes, R.* ; Liu, H.* ; Weihs, A.* ; Yu, Z.* ; Hoppmann, A.* ; Grundner-Culemann, F.* ; Min, J.L.* ; Adeyemo, A.A.* ; Agyemang, C.* ; Ärnlöv, J.* ; Aziz, N.A.* ; Baccarelli, A.* ; Bochud, M.* ; Brenner, H.* ; Breteler, M.M.B.* ; Carmeli, C.* ; Chaker, L.* ; Chambers, J.C.* ; Cole, S.A.* ; Coresh, J.* ; Corre, T.* ; Correa, A.* ; Cox, S.R.* ; de Klein, N.* ; Delgado, G.E.* ; Domingo-Relloso, A.* ; Eckardt, K.U.* ; Ekici, A.B.* ; Endlich, K.* ; Evans, K.L.* ; Floyd, J.S.* ; Fornage, M.* ; Franke, L.* ; Fraszczyk, E.* ; Gao, X.* ; Ghanbari, M.* ; Ghasemi, S.* ; Gieger, C. ; Greenland, P.* ; Grove, M.L.* ; Harris, S.E.* ; Hemani, G.* ; Henneman, P.* ; Herder, C.* ; Horvath, S.* ; Hou, L.* ; Hurme, M.A.* ; Hwang, S.J.* ; Jarvelin, M.R.* ; Kardia, S.L.R.* ; Kasela, S.* ; Kleber, M.E.* ; Koenig, W.* ; Kooner, J.S.* ; Kramer, H.* ; Kronenberg, F.* ; Kühnel, B. ; Lehtimäki, T.* ; Lind, L.* ; Liu, D.* ; Liu, Y.* ; Lloyd-Jones, D.M.* ; Lohman, K.* ; Lorkowski, S.* ; Lu, A.T.* ; Marioni, R.E.* ; März, W.* ; McCartney, D.L.* ; Meeks, K.A.C.* ; Milani, L.* ; Mishra, P.P.* ; Nauck, M.* ; Navas-Acien, A.* ; Nowak, C.* ; Peters, A. ; Prokisch, H. ; Psaty, B.M.* ; Raitakari, O.T.* ; Ratliff, S.M.* ; Reiner, A.P.* ; Rosas, S.E.* ; Schöttker, B.* ; Schwartz, J.* ; Sedaghat, S.* ; Smith, J.A.* ; Sotoodehnia, N.* ; Stocker, H.R.* ; Stringhini, S.* ; Sundström, J.* ; Swenson, B.R.* ; Tellez-Plaza, M.* ; van Meurs, J.B.J.* ; van Vliet-Ostaptchouk, J.V.* ; Venema, A.* ; Verweij, N.* ; Walker, R.M.* ; Wielscher, M.* ; Winkelmann, J. ; Wolffenbuttel, B.H.R.* ; Zhao, W.* ; Zheng, Y.* ; Estonian Biobank Research Team* ; Genetics of DNA Methylation Consortium* ; Loh, M.* ; Snieder, H.* ; Levy, D.* ; Waldenberger, M. ; Susztak, K.* ; Köttgen, A.* ; Teumer, A.*

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

Nat. Commun. 12:7174 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Glomerular-filtration-rate; Mendelian Randomization; Disease Gckd; Loci; Albuminuria; Management; Discovery; Haplotype; Elements; Outcomes
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 12, Heft: 1, Seiten: , Artikelnummer: 7174 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Epidemiology II (EPI2)
Institute of Neurogenomics (ING)
Förderungen Projekt DEAL