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

Nature Communications
Audrey Y ChuAnna Köttgen

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.

References

Sep 1, 1979·American Journal of Epidemiology·W B KannelW P Castelli
Dec 1, 1975·Preventive Medicine·M FeinleibW P Castelli
Apr 30, 2002·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·Josef CoreshAndrew S Levey
Sep 2, 2004·Journal of the American Society of Nephrology : JASN·Caroline S FoxDaniel Levy
Sep 24, 2005·American Journal of Nephrology·Barry I FreedmanWilliam M McClellan
May 6, 2009·Annals of Internal Medicine·Andrew S LeveyUNKNOWN CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration)
Apr 13, 2010·Nature Genetics·Anna KöttgenCaroline S Fox
Sep 25, 2010·Journal of the American Society of Nephrology : JASN·Michael Zeisberg, Eric G Neilson
Dec 15, 2010·Epigenetics : Official Journal of the DNA Methylation Society·Carmen SapienzaMichael Madaio
Jul 13, 2011·Nature Reviews. Genetics·Vardhman K RakyanStephan Beck
Apr 6, 2012·PLoS Genetics·Cristian PattaroCaroline S Fox
May 10, 2012·BMC Bioinformatics·Eugene Andres HousemanKarl T Kelsey
May 2, 2013·BMC Genomics·Ruth PidsleyLeonard C Schalkwyk
Nov 1, 2013·Kidney International·Jackie A FretzMark C Horowitz
Nov 2, 2013·Journal of the American Society of Nephrology : JASN·Katalin Susztak
Nov 21, 2013·Epigenetics : Official Journal of the DNA Methylation Society·Laura J SmythAmy Jayne McKnight
Feb 12, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Maria R WingUNKNOWN Chronic Renal Insufficiency Cohort (CRIC) Study
Mar 7, 2014·Molecular Biology Reports·Tian-Biao ZhouGregor P C Drummen
Aug 6, 2014·Clinical Journal of the American Society of Nephrology : CJASN·Rannveig SkrunesBjørn Egil Vikse
Sep 30, 2014·Nature Methods·Yassen AssenovChristoph Bock
Nov 19, 2014·The Journal of Biological Chemistry·Benoit DenhezPedro Geraldes
Nov 17, 2016·Cell Reports·Charles E BreezeStephan Beck

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Citations

Nov 21, 2017·Nature Reviews. Nephrology·Jack M Heintze
Apr 25, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Benjamin P LarkinSonia Saad
Feb 24, 2019·The Journal of Nutrition·Denise MafraPaul G Shiels
Mar 10, 2019·Journal of the American Society of Nephrology : JASN·Szu-Yuan LiKatalin Susztak
Feb 15, 2019·Journal of the American Society of Nephrology : JASN·Yuting GuanKatalin Susztak
May 9, 2019·Nature Reviews. Cardiology·Charlotte AnderssonRamachandran S Vasan
Sep 1, 2019·Current Diabetes Reports·Tamas Aranyi, Katalin Susztak
Nov 22, 2018·Disease Models & Mechanisms·Carmen Hurtado Del PozoNuria Montserrat
Nov 16, 2018·JCI Insight·Pietro E CippàAndrew P McMahon
May 16, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Adrienne Tin, Anna Köttgen
Mar 21, 2019·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Junyu ChenYan V Sun
Nov 23, 2019·Translational Psychiatry·Christiane ZieglerKatharina Domschke
Jun 7, 2019·JCI Insight·Jihwan ParkKatalin Susztak
Feb 23, 2020·Clinical Journal of the American Society of Nephrology : CJASN·Mark CanneySean J Barbour
May 20, 2020·Nature Reviews. Nephrology·Sean EddyMatthias Kretzler
May 28, 2020·Frontiers in Immunology·Rossana FranzinGiuseppe Castellano
Feb 8, 2019·Current Diabetes Reports·Lixia XuZhen Chen
Mar 22, 2019·Nature Reviews. Nephrology·Mitsuo Kato, Rama Natarajan
Jun 30, 2019·Current Diabetes Reports·Sangeeta Dhawan, Rama Natarajan
Jan 17, 2019·Mediators of Inflammation·Jose Luis Morgado-PascualSandra Rayego-Mateos
Jul 28, 2020·Genes·Diego Ingrosso, Alessandra F Perna
Jan 18, 2019·Nature Reviews. Nephrology·Chunyuan GuoZheng Dong
Oct 27, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Farah AmmousJennifer Smith
Nov 5, 2020·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Ashani LecamwasamRichard Saffery
Nov 13, 2020·Frontiers in Cell and Developmental Biology·Laura J SmythAmy Jayne McKnight
Dec 16, 2020·Epigenetics : Official Journal of the DNA Methylation Society·Yifei LinXueqing Yu
Jan 12, 2021·Free Radical Biology & Medicine·Gareth W DavisonColum P Walsh
Sep 3, 2019·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yan-Ni WangYing-Yong Zhao
Sep 10, 2020·Cytokine & Growth Factor Reviews·Anupama RaniSureshbabu Angara
Nov 5, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xin ShengKatalin Susztak
Nov 7, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Ju-Tao YuXiao-Ming Meng
Feb 25, 2021·Clinical Kidney Journal·Simona Ruxandra VolovatAdrian Covic

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Datasets Mentioned

BETA
GSM670025
GSM621648
GSM1112806

Methods Mentioned

BETA
biopsy
ChIP-seq
biopsies
chip
Assay

Software Mentioned

R
eForge
Minfi
IlluminaHumanMethylation450kanno
metafor
RnBeads
geepack R
lmekin R
lmer
qqman

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