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

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...

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Veröffentlicht in:Nature communications Jg. 8; H. 1; S. 1286 - 12
Hauptverfasser: Chu, Audrey Y., Tin, Adrienne, Schlosser, Pascal, Ko, Yi-An, Qiu, Chengxiang, Yao, Chen, Joehanes, Roby, Grams, Morgan E., Liang, Liming, Gluck, Caroline A., Liu, Chunyu, Coresh, Josef, Hwang, Shih-Jen, Levy, Daniel, Boerwinkle, Eric, Pankow, James S., Yang, Qiong, Fornage, Myriam, Fox, Caroline S., Susztak, Katalin, Köttgen, Anna
Format: Journal Article
Sprache:Englisch
Veröffentlicht: London Nature Publishing Group UK 03.11.2017
Nature Publishing Group
Nature Portfolio
Schlagworte:
631/208/176/1988
692/4022/272
Aged
Binding sites
Binding Sites - genetics
CCAAT-Enhancer-Binding Protein-beta - genetics
CCAAT-Enhancer-Binding Protein-beta - metabolism
CpG Islands
Deoxyribonucleic acid
Disease Progression
DNA
DNA methylation
DNA Methylation - genetics
E1A-Associated p300 Protein - genetics
E1A-Associated p300 Protein - metabolism
Enhancers
Epidermal growth factor receptors
Epigenesis, Genetic
Epigenetics
Female
Fibrosis
Genetic diversity
Genetic Predisposition to Disease
Genetic variance
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genotype & phenotype
Glomerular filtration rate
Glomerular Filtration Rate - genetics
Heart
Humanities and Social Sciences
Humans
Kidney - metabolism
Kidney diseases
Kidney transplantation
Kidneys
Male
Middle Aged
multidisciplinary
Prohibitins
Prospective Studies
Protein Tyrosine Phosphatase, Non-Receptor Type 6 - genetics
Protein Tyrosine Phosphatase, Non-Receptor Type 6 - metabolism
Regulatory mechanisms (biology)
Regulatory sequences
Renal cortex
Renal Insufficiency, Chronic - genetics
Renal Insufficiency, Chronic - physiopathology
Science
Science (multidisciplinary)
Studies
Trans-Activators - genetics
Trans-Activators - metabolism
Transcription Factors - genetics
Transcription Factors - metabolism
ISSN:2041-1723, 2041-1723
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Zusammenfassung: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. Genome-wide association studies of kidney function show enrichment of associated genetic variants in regulatory regions. Here, the authors perform epigenome-wide association studies of kidney function and disease, identifying 19 CpG sites significantly associated with these.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-017-01297-7