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

Schlosser P, Tin A, Matias-Garcia PR, Thio CHL, Joehanes R, Liu H, Weihs A, Yu Z, Hoppmann A, Grundner-Culemann F, Min JL, Adeyemo AA, Agyemang C, Arnlov J, Aziz NA, Baccarelli A, Bochud M, Brenner H, Breteler MMB, Carmeli C, Chaker L, Chambers JC, Cole SA, Coresh J, Corre T, Correa A, Cox SR, De Klein N, Delgado GE, Domingo-Relloso A, Eckardt KU, Ekici AB, Endlich K, Evans KL, Floyd JS, Fornage M, Franke L, Fraszczyk E, Gao X, Gao X, Ghanbari M, Ghasemi S, Gieger C, Greenland P, Grove ML, Harris SE, Hemani G, Henneman P, Herder C, Horvath S, Hou L, Hurme MA, Hwang SJ, Jarvelin MR, Kardia SLR, Kasela S, Kleber ME, Koenig W, Kooner JS, Kramer H, Kronenberg F, Kuhnel B, Lehtimaki T, Lind L, Liu D, Liu Y, Lloyd-Jones DM, Lohman K, Lorkowski S, Lu AT, Marioni RE, Marz W, Mccartney DL, Meeks KAC, Milani L, Mishra PP, Nauck M, Navas-Acien A, Nowak C, Peters A, Prokisch H, Psaty BM, Raitakari OT, Ratliff SM, Reiner AP, Rosas SE, Schottker B, Schwartz J, Sedaghat S, Smith JA, Sotoodehnia N, Stocker HR, Stringhini S, Sundstrom J, Swenson BR, Tellez-Plaza M, Van Meurs JBJ, Van Vliet-Ostaptchouk JV, Venema A, Verweij N, Walker RM, Wielscher M, Winkelmann J, Wolffenbuttel BHR, Zhao W, Zheng Y, Loh M, Snieder H, Levy D, Waldenberger M, Susztak K, Kottgen A, Teumer A (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Book Volume: 12

Journal Issue: 1

DOI: 10.1038/s41467-021-27234-3

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.

Authors with CRIS profile

Involved external institutions

Albert-Ludwigs-Universität Freiburg Germany (DE) Johns Hopkins University (JHU) United States (USA) (US) Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt (HMGU) / Helmholtz Munich Germany (DE) University of Groningen / Rijksuniversiteit Groningen Netherlands (NL) Framingham Heart Study United States (USA) (US) University of Pennsylvania United States (USA) (US) Universitätsmedizin Greifswald / Universitätsklinikum Greifswald Germany (DE) Eli and Edythe L. Broad Institute of MIT and Harvard United States (USA) (US) University of Bristol United Kingdom (GB) Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE) Germany (DE) Erasmus University Medical Center (MC) Netherlands (NL) University of Edinburgh United Kingdom (GB) University of Washington United States (USA) (US) McGovern Medical School United States (USA) (US) Columbia University United States (USA) (US) Deutsches Krebsforschungszentrum (DKFZ) Germany (DE) Northwestern University United States (USA) (US) University of Texas Health Science Center at Houston (UTHealth) United States (USA) (US) University of Amsterdam Netherlands (NL) Heinrich-Heine-Universität Düsseldorf Germany (DE) University of California Los Angeles (UCLA) United States (USA) (US) University of Michigan United States (USA) (US) Ruprecht-Karls-Universität Heidelberg Germany (DE) National Human Genome Research Institute (NHGRI) United States (USA) (US) University of Tartu Estonia (EE) University of Tampere (UTA) / Tampereen yliopisto (Tay) Finland (FI) Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK e.V.) Germany (DE) Karolinska Institute Sweden (SE) Université de Lausanne (UNIL) Switzerland (CH) Nanyang Technological University (NTU) Singapore (SG) Texas Biomedical Research Institute United States (USA) (US) University of Mississippi (Ole Miss) United States (USA) (US) Hospital Carlos III Spain (ES) Imperial College London / The Imperial College of Science, Technology and Medicine United Kingdom (GB) Technische Universität München (TUM) Germany (DE) London North West Healthcare NHS Trust United Kingdom (GB) Loyola University Chicago United States (USA) (US) Medizinische Universität Innsbruck Austria (AT) Uppsala University Sweden (SE) Duke University United States (USA) (US) Friedrich-Schiller-Universität Jena Germany (DE) University of Turku / Turun yliopisto Finland (FI) Veterans Affairs Healthcare System Boston and Harvard Medical School United States (USA) (US) Harvard University United States (USA) (US) University of Minnesota (UMN) United States (USA) (US)

How to cite

APA:

Schlosser, P., Tin, A., Matias-Garcia, P.R., Thio, C.H.L., Joehanes, R., Liu, H.,... Teumer, A. (2021). Meta-analyses identify DNA methylation associated with kidney function and damage. Nature Communications, 12(1). https://doi.org/10.1038/s41467-021-27234-3

MLA:

Schlosser, Pascal, et al. "Meta-analyses identify DNA methylation associated with kidney function and damage." Nature Communications 12.1 (2021).

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