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

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 L. Hanson, Robert G. Nelson, Katalin Susztak, Juliana C. N. Chan, Kevin Y. Yip () and Ronald C. W. Ma ()
Additional contact information
Kelly Yichen Li: The Chinese University of Hong Kong
Claudia Ha Ting Tam: The Chinese University of Hong Kong
Hongbo Liu: University of Pennsylvania
Samantha Day: National Institute of Diabetes and Digestive and Kidney Diseases
Cadmon King Poo Lim: The Chinese University of Hong Kong
Wing Yee So: The Chinese University of Hong Kong
Chuiguo Huang: The Chinese University of Hong Kong
Guozhi Jiang: The Chinese University of Hong Kong
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
Cheuk-Chun Szeto: 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
Juliana C. N. Chan: The Chinese University of Hong Kong
Kevin Y. Yip: The Chinese University of Hong Kong
Ronald C. W. Ma: The Chinese University of Hong Kong

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37837-7

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