1. A methylation risk score for chronic kidney disease: a HyperGEN study
- Author
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Jones, Alana C, Patki, Amit, Srinivasasainagendra, Vinodh, Hidalgo, Bertha A, Tiwari, Hemant K, Limdi, Nita A, Armstrong, Nicole D, Chaudhary, Ninad S, Minniefield, Bré, Absher, Devin, Arnett, Donna K, Lange, Leslie A, Lange, Ethan M, Young, Bessie A, Diamantidis, Clarissa J, Rich, Stephen S, Mychaleckyj, Josyf C, Rotter, Jerome I, Taylor, Kent D, Kramer, Holly J, Tracy, Russell P, Durda, Peter, Kasela, Silva, Lappalinen, Tuuli, Liu, Yongmei, Johnson, W Craig, Van Den Berg, David J, Franceschini, Nora, Liu, Simin, Mouton, Charles P, Bhatti, Parveen, Horvath, Steve, Whitsel, Eric A, and Irvin, Marguerite R
- Subjects
Epidemiology ,Biological Sciences ,Health Sciences ,Genetics ,Prevention ,Clinical Research ,Human Genome ,Health Disparities ,Kidney Disease ,Minority Health ,Women's Health ,2.1 Biological and endogenous factors ,4.1 Discovery and preclinical testing of markers and technologies ,Renal and urogenital ,Humans ,Renal Insufficiency ,Chronic ,DNA Methylation ,Male ,Female ,Middle Aged ,Glomerular Filtration Rate ,CpG Islands ,Risk Factors ,Black or African American ,Aged ,Genome-Wide Association Study ,Epigenesis ,Genetic ,Adult ,Genetic Predisposition to Disease ,Chronic kidney disease ,eGFR ,Methylation risk score ,Epigenetics - Abstract
Chronic kidney disease (CKD) impacts about 1 in 7 adults in the United States, but African Americans (AAs) carry a disproportionately higher burden of disease. Epigenetic modifications, such as DNA methylation at cytosine-phosphate-guanine (CpG) sites, have been linked to kidney function and may have clinical utility in predicting the risk of CKD. Given the dynamic relationship between the epigenome, environment, and disease, AAs may be especially sensitive to environment-driven methylation alterations. Moreover, risk models incorporating CpG methylation have been shown to predict disease across multiple racial groups. In this study, we developed a methylation risk score (MRS) for CKD in cohorts of AAs. We selected nine CpG sites that were previously reported to be associated with estimated glomerular filtration rate (eGFR) in epigenome-wide association studies to construct a MRS in the Hypertension Genetic Epidemiology Network (HyperGEN). In logistic mixed models, the MRS was significantly associated with prevalent CKD and was robust to multiple sensitivity analyses, including CKD risk factors. There was modest replication in validation cohorts. In summary, we demonstrated that an eGFR-based CpG score is an independent predictor of prevalent CKD, suggesting that MRS should be further investigated for clinical utility in evaluating CKD risk and progression.
- Published
- 2024