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Meta-analyses identify DNA methylation associated with kidney function and damage

Author

Listed:
  • Pascal Schlosser

    (Faculty of Medicine and Medical Center - University of Freiburg
    Johns Hopkins Bloomberg School of Public Health)

  • Adrienne Tin

    (Johns Hopkins Bloomberg School of Public Health
    University of Mississippi Medical Center)

  • Pamela R. Matias-Garcia

    (German Research Center for Environmental Health
    German Research Center for Environmental Health
    Technical University of Munich)

  • Chris H. L. Thio

    (University of Groningen, University Medical Center Groningen)

  • Roby Joehanes

    (Framingham Heart Study
    National Institutes of Health)

  • Hongbo Liu

    (University of Pennsylvania Perelman School of Medicine)

  • Antoine Weihs

    (University Medicine Greifswald)

  • Zhi Yu

    (Broad Institute
    Massachusetts General Hospital
    Massachusetts General Hospital)

  • Anselm Hoppmann

    (Faculty of Medicine and Medical Center - University of Freiburg)

  • Franziska Grundner-Culemann

    (Faculty of Medicine and Medical Center - University of Freiburg)

  • Josine L. Min

    (University of Bristol
    University of Bristol)

  • Adebowale A. Adeyemo

    (National Institutes of Health)

  • Charles Agyemang

    (University of Amsterdam)

  • Johan Ärnlöv

    (Karolinska Institutet
    Dalarna University)

  • Nasir A. Aziz

    (German Centre for Neurodegenerative Diseases (DZNE)
    University of Bonn)

  • Andrea Baccarelli

    (Columbia University)

  • Murielle Bochud

    (University of Lausanne)

  • Hermann Brenner

    (Division of Clinical Epidemiology and Aging Research
    Heidelberg University
    German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT)
    German Cancer Research Center (DKFZ))

  • Monique M. B. Breteler

    (German Centre for Neurodegenerative Diseases (DZNE)
    University of Bonn)

  • Cristian Carmeli

    (University of Lausanne
    University of Fribourg)

  • Layal Chaker

    (Erasmus University Medical Center
    Erasmus Medical Center)

  • John C. Chambers

    (Nanyang Technological University
    Imperial College London
    London North West Healthcare NHS Trust
    Imperial College Healthcare NHS Trust)

  • Shelley A. Cole

    (Texas Biomedical Research Institute)

  • Josef Coresh

    (Johns Hopkins Bloomberg School of Public Health)

  • Tanguy Corre

    (University of Lausanne)

  • Adolfo Correa

    (University of Mississippi Medical Center)

  • Simon R. Cox

    (The University of Edinburgh)

  • Niek Klein

    (University Medical Center Groningen, University of Groningen)

  • Graciela E. Delgado

    (Heidelberg University)

  • Arce Domingo-Relloso

    (Carlos III Health Institute
    Columbia University Mailman School of Public Health
    University of Valencia)

  • Kai-Uwe Eckardt

    (University of Erlangen-Nürnberg
    Charité - Universitätsmedizin Berlin)

  • Arif B. Ekici

    (Friedrich-Alexander-UniversitätErlangen-Nürnberg)

  • Karlhans Endlich

    (University Medicine Greifswald
    Partner Site Greifswald)

  • Kathryn L. Evans

    (University of Edinburgh)

  • James S. Floyd

    (University of Washington
    University of Washington
    University of Washington)

  • Myriam Fornage

    (McGovern Medical School
    The University of Texas Health Science Center at Houston)

  • Lude Franke

    (University Medical Center Groningen, University of Groningen
    Oncode Institute)

  • Eliza Fraszczyk

    (University of Groningen, University Medical Center Groningen)

  • Xu Gao

    (Columbia University
    Peking University)

  • Xīn Gào

    (Division of Clinical Epidemiology and Aging Research)

  • Mohsen Ghanbari

    (Erasmus University Medical Center)

  • Sahar Ghasemi

    (University Medicine Greifswald
    Partner Site Greifswald
    University Medicine Greifswald)

  • Christian Gieger

    (German Research Center for Environmental Health
    German Research Center for Environmental Health)

  • Philip Greenland

    (Northwestern University Feinberg School of Medicine)

  • Megan L. Grove

    (The University of Texas Health Science Center at Houston)

  • Sarah E. Harris

    (The University of Edinburgh)

  • Gibran Hemani

    (University of Bristol
    University of Bristol)

  • Peter Henneman

    (Amsterdam University Medical Centres, University of Amsterdam)

  • Christian Herder

    (Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf
    German Center for Diabetes Research
    Medical Faculty and University Hospital Düsseldorf, Heinrich Heine University Düsseldorf)

  • Steve Horvath

    (University of California Los Angeles
    Biostatistics, Fielding School of Public Health, UCLA)

  • Lifang Hou

    (Northwestern University Feinberg School of Medicine)

  • Mikko A. Hurme

    (Tampere University)

  • Shih-Jen Hwang

    (Framingham Heart Study
    National Institutes of Health)

  • Marjo-Riitta Jarvelin

    (Imperial College London
    University of Oulu
    University of Oulu
    Oulu University Hospital)

  • Sharon L. R. Kardia

    (University of Michigan)

  • Silva Kasela

    (University of Tartu)

  • Marcus E. Kleber

    (Heidelberg University
    SYNLAB MVZ Humangenetik Mannheim)

  • Wolfgang Koenig

    (Technische Universität München
    Partner site Munich Heart Alliance
    University of Ulm)

  • Jaspal S. Kooner

    (London North West Healthcare NHS Trust
    Imperial College Healthcare NHS Trust
    Imperial College London)

  • Holly Kramer

    (Loyola University Chicago
    Edward Hines VA Medical Center)

  • Florian Kronenberg

    (Medical University of Innsbruck)

  • Brigitte Kühnel

    (German Research Center for Environmental Health
    German Research Center for Environmental Health)

  • Terho Lehtimäki

    (Tampere University
    Tampere University
    Fimlab Laboratories)

  • Lars Lind

    (Uppsala University)

  • Dan Liu

    (German Centre for Neurodegenerative Diseases (DZNE))

  • Yongmei Liu

    (Duke University School of Medicine)

  • Donald M. Lloyd-Jones

    (Northwestern University Feinberg School of Medicine)

  • Kurt Lohman

    (Duke University School of Medicine)

  • Stefan Lorkowski

    (Friedrich Schiller University Jena
    Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig)

  • Ake T. Lu

    (University of California Los Angeles)

  • Riccardo E. Marioni

    (University of Edinburgh)

  • Winfried März

    (Heidelberg University
    Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig
    Synlab Academy, SYNLAB Holding Deutschland GmbH, Mannheim and Augsburg
    Medical University of Graz)

  • Daniel L. McCartney

    (University of Edinburgh)

  • Karlijn A. C. Meeks

    (National Institutes of Health
    University of Amsterdam)

  • Lili Milani

    (University of Tartu)

  • Pashupati P. Mishra

    (Tampere University
    Tampere University
    Fimlab Laboratories)

  • Matthias Nauck

    (Partner Site Greifswald
    University Medicine Greifswald)

  • Ana Navas-Acien

    (Columbia University Mailman School of Public Health)

  • Christoph Nowak

    (Karolinska Institutet)

  • Annette Peters

    (German Research Center for Environmental Health
    Ludwig-Maximilians Universität München)

  • Holger Prokisch

    (Technische Universität München
    Helmholtz Zentrum München)

  • Bruce M. Psaty

    (University of Washington
    University of Washington
    University of Washington
    University of Washington)

  • Olli T. Raitakari

    (University of Turku
    Turku University Hospital
    University of Turku and Turku University Hospital)

  • Scott M. Ratliff

    (University of Michigan)

  • Alex P. Reiner

    (University of Washington)

  • Sylvia E. Rosas

    (Joslin Diabetes Center
    Harvard Medical School)

  • Ben Schöttker

    (Division of Clinical Epidemiology and Aging Research
    Heidelberg University)

  • Joel Schwartz

    (Harvard T.H. Chan School of Public Health)

  • Sanaz Sedaghat

    (University of Minnesota)

  • Jennifer A. Smith

    (University of Michigan
    University of Michigan)

  • Nona Sotoodehnia

    (University of Washington)

  • Hannah R. Stocker

    (Division of Clinical Epidemiology and Aging Research
    Heidelberg University)

  • Silvia Stringhini

    (University of Lausanne)

  • Johan Sundström

    (Uppsala University
    University of New South Wales)

  • Brenton R. Swenson

    (University of Washington
    University of Washington)

  • Maria Tellez-Plaza

    (Carlos III Health Institute)

  • Joyce B. J. Meurs

    (Erasmus Medical Center)

  • Jana V. Vliet-Ostaptchouk

    (University of Groningen, University Medical Center Groningen)

  • Andrea Venema

    (Amsterdam University Medical Centres, University of Amsterdam)

  • Niek Verweij

    (University Medical Center Groningen, University of Groningen)

  • Rosie M. Walker

    (University of Edinburgh)

  • Matthias Wielscher

    (Imperial College London)

  • Juliane Winkelmann

    (Technische Universität München
    Helmholtz Zentrum München
    Technische Universität München
    Munich Cluster for Systems Neurology (SyNergy))

  • Bruce H. R. Wolffenbuttel

    (University of Groningen, University Medical Center Groningen)

  • Wei Zhao

    (University of Michigan)

  • Yinan Zheng

    (Northwestern University Feinberg School of Medicine)

  • Marie Loh

    (Nanyang Technological University
    Imperial College London)

  • Harold Snieder

    (University of Groningen, University Medical Center Groningen)

  • Daniel Levy

    (Framingham Heart Study
    National Institutes of Health)

  • Melanie Waldenberger

    (German Research Center for Environmental Health
    German Research Center for Environmental Health
    Partner site Munich Heart Alliance)

  • Katalin Susztak

    (University of Pennsylvania Perelman School of Medicine)

  • Anna Köttgen

    (Faculty of Medicine and Medical Center - University of Freiburg
    Johns Hopkins Bloomberg School of Public Health)

  • Alexander Teumer

    (Partner Site Greifswald
    University Medicine Greifswald
    Medical University of Bialystok)

Abstract

Chronic kidney disease is a major public health burden. Elevated urinary albumin-to-creatinine ratio is a measure of kidney damage, and used to diagnose and stage chronic kidney disease. To extend the knowledge on regulatory mechanisms related to kidney function and disease, we conducted a blood-based epigenome-wide association study for estimated glomerular filtration rate (n = 33,605) and urinary albumin-to-creatinine ratio (n = 15,068) and detected 69 and seven CpG sites where DNA methylation was associated with the respective trait. The majority of these findings showed directionally consistent associations with the respective clinical outcomes chronic kidney disease and moderately increased albuminuria. Associations of DNA methylation with kidney function, such as CpGs at JAZF1, PELI1 and CHD2 were validated in kidney tissue. Methylation at PHRF1, LDB2, CSRNP1 and IRF5 indicated causal effects on kidney function. Enrichment analyses revealed pathways related to hemostasis and blood cell migration for estimated glomerular filtration rate, and immune cell activation and response for urinary albumin-to-creatinineratio-associated CpGs.

Suggested Citation

  • Pascal Schlosser & Adrienne Tin & Pamela R. Matias-Garcia & Chris H. L. Thio & Roby Joehanes & Hongbo Liu & Antoine Weihs & Zhi Yu & Anselm Hoppmann & Franziska Grundner-Culemann & Josine L. Min & Ade, 2021. "Meta-analyses identify DNA methylation associated with kidney function and damage," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27234-3
    DOI: 10.1038/s41467-021-27234-3
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    References listed on IDEAS

    as
    1. Alexander Teumer & Yong Li & Sahar Ghasemi & Bram P. Prins & Matthias Wuttke & Tobias Hermle & Ayush Giri & Karsten B. Sieber & Chengxiang Qiu & Holger Kirsten & Adrienne Tin & Audrey Y. Chu & Nisha B, 2019. "Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria," Nature Communications, Nature, vol. 10(1), pages 1-19, December.
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    2. Thomas Battram & Tom R. Gaunt & Caroline L. Relton & Nicholas J. Timpson & Gibran Hemani, 2022. "A comparison of the genes and genesets identified by GWAS and EWAS of fifteen complex traits," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    3. Yu Yan & Hongbo Liu & Amin Abedini & Xin Sheng & Matthew Palmer & Hongzhe Li & Katalin Susztak, 2024. "Unraveling the epigenetic code: human kidney DNA methylation and chromatin dynamics in renal disease development," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
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