Chu, Audrey Y.Tin, AdrienneSchlosser, PascalKo, Yi-AnQiu, ChengxiangYao, ChenJoehanes, RobyGrams, Morgan E.Liang, LimingGluck, Caroline A.Liu, ChunyuCoresh, JosefHwang, Shih-JenLevy, DanielBoerwinkle, EricPankow, James S.Yang, QiongFornage, MyriamFox, Caroline S.Susztak, KatalinKöttgen, Anna2017-12-062017Chu, A. Y., A. Tin, P. Schlosser, Y. Ko, C. Qiu, C. Yao, R. Joehanes, et al. 2017. “Epigenome-wide association studies identify DNA methylation associated with kidney function.” Nature Communications 8 (1): 1286. doi:10.1038/s41467-017-01297-7. http://dx.doi.org/10.1038/s41467-017-01297-7.http://nrs.harvard.edu/urn-3:HUL.InstRepos:34493249Chronic 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.en-USJournal Article2017-12-0610.1038/s41467-017-01297-7