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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Vydáno v:	Nature communications Ročník 8; číslo 1; s. 1286 - 12
Hlavní autoři:	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
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 03.11.2017 Nature Publishing Group Nature Portfolio
Témata:	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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Shrnutí:	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.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 ObjectType-Undefined-3
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-017-01297-7