Dataset Information

A methylation risk score for chronic kidney disease: a HyperGEN study.

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.

SUBMITTER: Jones AC

PROVIDER: S-EPMC11291488 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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A methylation risk score for chronic kidney disease: a HyperGEN study.

Jones Alana C AC Patki Amit A Srinivasasainagendra Vinodh V Hidalgo Bertha A BA Tiwari Hemant K HK Limdi Nita A NA Armstrong Nicole D ND Chaudhary Ninad S NS Minniefield Bré B Absher Devin D Arnett Donna K DK Lange Leslie A LA Lange Ethan M EM Young Bessie A BA Diamantidis Clarissa J CJ Rich Stephen S SS Mychaleckyj Josyf C JC Rotter Jerome I JI Taylor Kent D KD Kramer Holly J HJ Tracy Russell P RP Durda Peter P Kasela Silva S Lappalinen Tuuli T Liu Yongmei Y Johnson W Craig WC Van Den Berg David J DJ Franceschini Nora N Liu Simin S Mouton Charles P CP Bhatti Parveen P Horvath Steve S Whitsel Eric A EA Irvin Marguerite R MR

Scientific reports 20240801 1

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 alte ...[more]

PMID: 39085340

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Project description:BackgroundChronic Kidney Disease (CKD) represents a great burden for the patient and the health system, particularly if diagnosed at late stages. Consequently, tools to identify patients at high risk of having CKD are needed, particularly in limited-resources settings where laboratory facilities are scarce. This study aimed to develop a risk score for prevalent undiagnosed CKD using data from four settings in Peru: a complete risk score including all associated risk factors and another excluding laboratory-based variables.MethodsCross-sectional study. We used two population-based studies: one for developing and internal validation (CRONICAS), and another (PREVENCION) for external validation. Risk factors included clinical- and laboratory-based variables, among others: sex, age, hypertension and obesity; and lipid profile, anemia and glucose metabolism. The outcome was undiagnosed CKD: eGFR < 60 ml/min/1.73m2. We tested the performance of the risk scores using the area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, positive/negative predictive values and positive/negative likelihood ratios.ResultsParticipants in both studies averaged 57.7 years old, and over 50% were females. Age, hypertension and anemia were strongly associated with undiagnosed CKD. In the external validation, at a cut-off point of 2, the complete and laboratory-free risk scores performed similarly well with a ROC area of 76.2% and 76.0%, respectively (P = 0.784). The best assessment parameter of these risk scores was their negative predictive value: 99.1% and 99.0% for the complete and laboratory-free, respectively.ConclusionsThe developed risk scores showed a moderate performance as a screening test. People with a score of ≥ 2 points should undergo further testing to rule out CKD. Using the laboratory-free risk score is a practical approach in developing countries where laboratories are not readily available and undiagnosed CKD has significant morbidity and mortality.

Dataset Information

A methylation risk score for chronic kidney disease: a HyperGEN study.

Publications

A methylation risk score for chronic kidney disease: a HyperGEN study.

Similar Datasets

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