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Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease

Author

Listed:
  • Laura J. Smyth

    (Queen’s University Belfast)

  • Emma H. Dahlström

    (Folkhälsan Research Center
    University of Helsinki and Helsinki University Hospital
    University of Helsinki)

  • Anna Syreeni

    (Folkhälsan Research Center
    University of Helsinki and Helsinki University Hospital
    University of Helsinki)

  • Katie Kerr

    (Queen’s University Belfast)

  • Jill Kilner

    (Queen’s University Belfast)

  • Ross Doyle

    (University College Dublin)

  • Eoin Brennan

    (University College Dublin)

  • Viji Nair

    (University of Michigan School of Medicine)

  • Damian Fermin

    (University of Michigan School of Medicine)

  • Robert G. Nelson

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Helen C. Looker

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Christopher Wooster

    (Queen’s University Belfast)

  • Darrell Andrews

    (University College Dublin)

  • Kerry Anderson

    (Queen’s University Belfast)

  • Gareth J. McKay

    (Queen’s University Belfast)

  • Joanne B. Cole

    (Broad Institute
    Massachusetts General Hospital)

  • Rany M. Salem

    (University of California San Diego)

  • Peter J. Conlon

    (Beaumont Hospital and Department of Medicine Royal College of Surgeons in Ireland)

  • Matthias Kretzler

    (University of Michigan)

  • Joel N. Hirschhorn

    (Broad Institute
    Boston Children’s Hospital
    Harvard Medical School)

  • Denise Sadlier

    (Mater Misericordiae Hospital)

  • Catherine Godson

    (University College Dublin)

  • Jose C. Florez

    (Broad Institute
    Massachusetts General Hospital
    Harvard Medical School)

  • Carol Forsblom

    (Folkhälsan Research Center
    University of Helsinki and Helsinki University Hospital
    University of Helsinki)

  • Alexander P. Maxwell

    (Queen’s University Belfast
    Belfast City Hospital)

  • Per-Henrik Groop

    (Folkhälsan Research Center
    University of Helsinki and Helsinki University Hospital
    University of Helsinki
    Monash University)

  • Niina Sandholm

    (Folkhälsan Research Center
    University of Helsinki and Helsinki University Hospital
    University of Helsinki)

  • Amy Jayne McKnight

    (Queen’s University Belfast)

Abstract

Type 1 diabetes affects over nine million individuals globally, with approximately 40% developing diabetic kidney disease. Emerging evidence suggests that epigenetic alterations, such as DNA methylation, are involved in diabetic kidney disease. Here we assess differences in blood-derived genome-wide DNA methylation associated with diabetic kidney disease in 1304 carefully characterised individuals with type 1 diabetes and known renal status from two cohorts in the United Kingdom-Republic of Ireland and Finland. In the meta-analysis, we identify 32 differentially methylated CpGs in diabetic kidney disease in type 1 diabetes, 18 of which are located within genes differentially expressed in kidneys or correlated with pathological traits in diabetic kidney disease. We show that methylation at 21 of the 32 CpGs predict the development of kidney failure, extending the knowledge and potentially identifying individuals at greater risk for diabetic kidney disease in type 1 diabetes.

Suggested Citation

  • Laura J. Smyth & Emma H. Dahlström & Anna Syreeni & Katie Kerr & Jill Kilner & Ross Doyle & Eoin Brennan & Viji Nair & Damian Fermin & Robert G. Nelson & Helen C. Looker & Christopher Wooster & Darrel, 2022. "Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34963-6
    DOI: 10.1038/s41467-022-34963-6
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    References listed on IDEAS

    as
    1. 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.
    2. Audrey Y. Chu & Adrienne Tin & Pascal Schlosser & Yi-An Ko & Chengxiang Qiu & Chen Yao & Roby Joehanes & Morgan E. Grams & Liming Liang & Caroline A. Gluck & Chunyu Liu & Josef Coresh & Shih-Jen Hwang, 2017. "Epigenome-wide association studies identify DNA methylation associated with kidney function," Nature Communications, Nature, vol. 8(1), pages 1-12, December.
    3. Niina Sandholm & Rany M Salem & Amy Jayne McKnight & Eoin P Brennan & Carol Forsblom & Tamara Isakova & Gareth J McKay & Winfred W Williams & Denise M Sadlier & Ville-Petteri Mäkinen & Elizabeth J Swa, 2012. "New Susceptibility Loci Associated with Kidney Disease in Type 1 Diabetes," PLOS Genetics, Public Library of Science, vol. 8(9), pages 1-13, September.
    4. Adrienne Tin & Pascal Schlosser & Pamela R. Matias-Garcia & Chris H. L. Thio & Roby Joehanes & Hongbo Liu & Zhi Yu & Antoine Weihs & Anselm Hoppmann & Franziska Grundner-Culemann & Josine L. Min & Vic, 2021. "Epigenome-wide association study of serum urate reveals insights into urate co-regulation and the SLC2A9 locus," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
    5. Caroline Gluck & Chengxiang Qiu & Sang Youb Han & Matthew Palmer & Jihwan Park & Yi-An Ko & Yuting Guan & Xin Sheng & Robert L. Hanson & Jing Huang & Yong Chen & Ae Seo Deok Park & Maria Concepcion Iz, 2019. "Kidney cytosine methylation changes improve renal function decline estimation in patients with diabetic kidney disease," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
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