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Nat Commun. 2017 Nov 3;8(1):1286. doi: 10.1038/s41467-017-01297-7.

Epigenome-wide association studies identify DNA methylation associated with kidney function.

Author information

1
The Population Sciences Branch, Division of Intramural Research, NHLBI, NIH, Bethesda, MD, 20892, USA.
2
NHLBI's Framingham Heart Study, Framingham, MA, 01702, USA.
3
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA.
4
Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, 79106, Freiburg, Germany.
5
Renal Electrolyte and Hypertension Division, Department of Medicine, Department of Genetics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
6
Institute of Aging Research, Hebrew Senior Life, Boston, MA, 02131, USA.
7
Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, 02215, USA.
8
Department of Biostatistics, Harvard University School of Public Health, Boston, MA, 02115, USA.
9
Human Genetics Center, University of Texas Health Science Center, Houston, TX, 77030, USA.
10
Division of Epidemiology & Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, 55454, USA.
11
Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
12
Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, 21205, USA. anna.koettgen@uniklinik-freiburg.de.
13
Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center-University of Freiburg, 79106, Freiburg, Germany. anna.koettgen@uniklinik-freiburg.de.

Abstract

Chronic kidney disease (CKD) is defined by reduced estimated glomerular filtration rate (eGFR). Previous genetic studies have implicated regulatory mechanisms contributing to CKD. Here we present epigenome-wide association studies of eGFR and CKD using whole-blood DNA methylation of 2264 ARIC Study and 2595 Framingham Heart Study participants to identify epigenetic signatures of kidney function. Of 19 CpG sites significantly associated (P < 1e-07) with eGFR/CKD and replicated, five also associate with renal fibrosis in biopsies from CKD patients and show concordant DNA methylation changes in kidney cortex. Lead CpGs at PTPN6/PHB2, ANKRD11, and TNRC18 map to active enhancers in kidney cortex. At PTPN6/PHB2 cg19942083, methylation in kidney cortex associates with lower renal PTPN6 expression, higher eGFR, and less renal fibrosis. The regions containing the 243 eGFR-associated (P < 1e-05) CpGs are significantly enriched for transcription factor binding sites of EBF1, EP300, and CEBPB (P < 5e-6). Our findings highlight kidney function associated epigenetic variation.

PMID:
29097680
PMCID:
PMC5668367
DOI:
10.1038/s41467-017-01297-7
[Indexed for MEDLINE]
Free PMC Article

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