Meta-analyses identify DNA methylation associated with kidney function and damage.
Nat Commun. 2021 Dec 9;12(1):7174. doi: 10.1038/s41467-021-27234-3. PMID: 34887417.
| Authors/Editors: | 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, Ärnlöv 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, Gào 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, Kühnel B, Lehtimäki T, Lind L, Liu D, Liu Y, Lloyd-Jones DM, Lohman K, Lorkowski S, Lu AT, Marioni RE, März 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, Schöttker B, Schwartz J, Sedaghat S, Smith JA, Sotoodehnia N, Stocker HR, Stringhini S, Sundström 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; Estonian Biobank Research Team; Genetics of DNA Methylation Consortium, Loh M, Snieder H, Levy D, Waldenberger M, Susztak K, Köttgen A, Teumer A. |
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| Publication Date: | 2021 |
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.
