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DNA methylation markers for kidney function and progression of diabetic kidney disease

Author

Listed:
  • Kelly Yichen Li

    (The Chinese University of Hong Kong
    Sanford Burnham Prebys Medical Discovery Institute)

  • Claudia Ha Ting Tam

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Hongbo Liu

    (University of Pennsylvania
    University of Pennsylvania)

  • Samantha Day

    (National Institute of Diabetes and Digestive and Kidney Diseases
    Midwestern University)

  • Cadmon King Poo Lim

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Wing Yee So

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Chuiguo Huang

    (The Chinese University of Hong Kong)

  • Guozhi Jiang

    (The Chinese University of Hong Kong
    Sun Yat-sen University)

  • Mai Shi

    (The Chinese University of Hong Kong)

  • Heung Man Lee

    (The Chinese University of Hong Kong)

  • Hui-yao Lan

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Cheuk-Chun Szeto

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Robert L. Hanson

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Robert G. Nelson

    (National Institute of Diabetes and Digestive and Kidney Diseases)

  • Katalin Susztak

    (University of Pennsylvania
    University of Pennsylvania)

  • Juliana C. N. Chan

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Kevin Y. Yip

    (The Chinese University of Hong Kong
    Sanford Burnham Prebys Medical Discovery Institute
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

  • Ronald C. W. Ma

    (The Chinese University of Hong Kong
    The Chinese University of Hong Kong
    The Chinese University of Hong Kong)

Abstract

Epigenetic markers are potential biomarkers for diabetes and related complications. Using a prospective cohort from the Hong Kong Diabetes Register, we perform two independent epigenome-wide association studies to identify methylation markers associated with baseline estimated glomerular filtration rate (eGFR) and subsequent decline in kidney function (eGFR slope), respectively, in 1,271 type 2 diabetes subjects. Here we show 40 (30 previously unidentified) and eight (all previously unidentified) CpG sites individually reach epigenome-wide significance for baseline eGFR and eGFR slope, respectively. We also develop a multisite analysis method, which selects 64 and 37 CpG sites for baseline eGFR and eGFR slope, respectively. These models are validated in an independent cohort of Native Americans with type 2 diabetes. Our identified CpG sites are near genes enriched for functional roles in kidney diseases, and some show association with renal damage. This study highlights the potential of methylation markers in risk stratification of kidney disease among type 2 diabetes individuals.

Suggested Citation

  • Kelly Yichen Li & Claudia Ha Ting Tam & Hongbo Liu & Samantha Day & Cadmon King Poo Lim & Wing Yee So & Chuiguo Huang & Guozhi Jiang & Mai Shi & Heung Man Lee & Hui-yao Lan & Cheuk-Chun Szeto & Robert, 2023. "DNA methylation markers for kidney function and progression of diabetic kidney disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37837-7
    DOI: 10.1038/s41467-023-37837-7
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    References listed on IDEAS

    as
    1. 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.
    2. 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.
    3. 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.
    4. Kira J. Stanzick & Yong Li & Pascal Schlosser & Mathias Gorski & Matthias Wuttke & Laurent F. Thomas & Humaira Rasheed & Bryce X. Rowan & Sarah E. Graham & Brett R. Vanderweff & Snehal B. Patil & Cass, 2021. "Discovery and prioritization of variants and genes for kidney function in >1.2 million individuals," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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