Abstract: TH-PO458
Genome-Wide DNA Methylation Association Study Identifies DNA Methylation Associated with ESRD
Session Information
- Genetic Diseases: Glomerulopathies - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic
Author
- Zhou, Xiaohong, Guangdong Provincial People's Hospital, Guangzhou, Guangdong, China
Background
Kidney disease is a progressive condition afflicting >10% of the general population worldwide, of which progression to end-stage renal disease (ESRD) caused poor quality of life and significant premature mortality. Defining DNA methylation biomarkers and understanding their roles in ESRD may help develop preventive and therapeutic strategies for kidney disease progression.
Methods
We conduct a blood-based genome-wide DNA methylation association study of ESRD in 2 independent cohorts (consisting of 1924 samples) from China and Singapore. Two-sample summary-level Mendelian randomization analysis was performed to evaluate the causality of the associations between methylation at DMP and kidney function (eGFR/eGFR decline). We also attempted to identify the candidates of ESRD-related genes underlying the significant associations by integrating the regulatory information from multiple public and published datasets. Using publicly available tools, we analyzed drug candidates for prevention or treatment of CKD progression based on ESRD-related genes.
Results
We identified a total of 922 differentially methylated positions (DMPs) at genome-wide significance (P < 9e-8). Regulatory function analysis of these DMPs have implicated 1255 candidate ESRD-related genes, which are enriched for biological processes related to immunity, GTPase activator activity, and signal complex assembly. All the candidate genes were enriched in key regulatory elements for gene function, including accessible chromatin elements. Of these candidate ESRD-related genes, some are the targets of investigational or approved drugs. Mendelian randomization revealed some causal association between DMPs and kidney function (eGFR/eGFR decline).
Conclusion
Our study demonstrated that DNA methylation play a significant role in the progression of kidney disease. Our study has not only identified DMPs as potential biomarkers for predicting renal progression and further implicated genes as potential therapeutic targets for ESRD treatment.
Funding
- Government Support – Non-U.S.