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

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

Object Details

• Location: Deutsche Nationalbibliothek Frankfurt am Main
• Extent: Online-Ressource
• Language: Englisch
• Notes: Nature Communications. - 8 (2017) , 1286, ISSN: 2041-1723

Contributors, Places and Time

• Event: Veröffentlichung
• (where): Freiburg
• (who): Universität
• (when): 2019
• Creator: Chu, Audrey Y. ; Tin, Adrienne ; Schlosser, Pascal ; Ko, Yi-An ; Qiu, Chengxiang ; Yao, Chen ; Joehanes, Roby ; Grams, Morgan E. ; Liang, Liming ; Gluck, Caroline ; Liu, Chunyu ; Coresh, Josef ; Hwang, Shih-Jen ; Levy, Daniel ; Boerwinkle, Eric ; Pankow, James ; Yang, Qiong ; Fornage, Myriam ; Fox, Caroline S. ; Susztak, Katalin ; Köttgen, Anna

Further information

• DOI: 10.1038/s41467-017-01297-7
• URN: urn:nbn:de:bsz:25-freidok-1418689
• Rights: Kein Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
• Last update: 25.03.2025, 1:49 PM CET