ArticleScience translational medicine2024
Integrated analysis of blood DNA methylation, genetic variants, circulating proteins, microRNAs, and kidney failure in type 1 diabetes.
Article in Science translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed.
- Genome-wide DNA methylation analysis revealed epigenetic mechanism underlying end-stage renal disease.Nature communications · 2026Article
- Blood DNA methylation markers are associated with diabetic kidney disease progression in type 1 diabetes.Diabetologia · 2026Article
- New potential therapeutic targets of metabolic disorder-associated kidney disease and diabetic kidney disease.Kidney international · 2026Review
- Environmental Mechanisms Influencing the Pathogenesis and Progression of Type 1 Diabetes.International journal of molecular sciences · 2025Review
- Genetic Determinants of Chronic Kidney Disease (CKD) in India: A Comprehensive Genomewide Association Study (GWAS) Analysis.International journal of nephrology · 2025Article
- Multi-Omics Integration in Nephrology: Advances, Challenges, and Future Directions.Seminars in nephrology · 2024Review
- Update: the role of epigenetics in the metabolic memory of diabetic complications.American journal of physiology. Renal physiology · 2024Review
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
Variation in DNA methylation (DNAmet) in white blood cells and other cells/tissues has been implicated in the etiology of progressive diabetic kidney disease (DKD). However, the specific mechanisms linking DNAmet variation in blood cells with risk of kidney failure (KF) and utility of measuring blood cell DNAmet in personalized medicine are not clear. We measured blood cell DNAmet in 277 individuals with type 1 diabetes and DKD using Illumina EPIC arrays; 51% of the cohort developed KF during 7 to 20 years of follow-up. Our epigenome-wide analysis identified DNAmet at 17 CpGs (5'-cytosine-phosphate-guanine-3' loci) associated with risk of KF independent of major clinical risk factors. DNAmet at these KF-associated CpGs remained stable over a median period of 4.7 years. Furthermore, DNAmet variations at seven KF-associated CpGs were strongly associated with multiple genetic variants at seven genomic regions, suggesting a strong genetic influence on DNAmet. The effects of DNAmet variations at the KF-associated CpGs on risk of KF were partially mediated by multiple KF-associated circulating proteins and KF-associated circulating miRNAs. A prediction model for risk of KF was developed by adding blood cell DNAmet at eight selected KF-associated CpGs to the clinical model. This updated model significantly improved prediction performance (c-statistic = 0.93) versus the clinical model (c-statistic = 0.85) at
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.