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

Autor: Jones AC; Medical Scientist Training Program, University of Alabama at Birmingham, 912 18th St S, Birmingham, AL, 35233, USA. acjones@uab.edu.; Department of Epidemiology, University of Alabama at Birmingham, 912 18th St S, Birmingham, AL, 35233, USA. acjones@uab.edu., Patki A; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Srinivasasainagendra V; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Hidalgo BA; Department of Epidemiology, University of Alabama at Birmingham, 912 18th St S, Birmingham, AL, 35233, USA., Tiwari HK; Department of Biostatistics, University of Alabama at Birmingham, Birmingham, AL, USA., Limdi NA; Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, USA., Armstrong ND; Department of Epidemiology, University of Alabama at Birmingham, 912 18th St S, Birmingham, AL, 35233, USA., Chaudhary NS; 23andMe, South San Francisco, CA, USA., Minniefield B; Department of Biology, Florida State University-Panama City, Panama City, FL, USA., Absher D; HudsonAlpha Institute for Biotechnology, Huntsville, AL, USA., Arnett DK; Office of the Provost, University of South Carolina, Columbia, SC, USA., Lange LA; Department of Biomedical Informatics, University of Colorado-Anschutz, Aurora, CO, USA., Lange EM; Department of Biomedical Informatics, University of Colorado-Anschutz, Aurora, CO, USA., Young BA; Division of Nephrology, University of Washington, Seattle, WA, USA., Diamantidis CJ; Department of Medicine, Duke University School of Medicine, Durham, NC, USA., Rich SS; Department of Genome Sciences, University of Virginia, Charlottesville, VA, USA., Mychaleckyj JC; Department of Public Health Sciences, Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Rotter JI; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Taylor KD; The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA., Kramer HJ; Departments of Public Health Sciences and Medicine, Loyola University Medical Center, Taywood, IL, USA., Tracy RP; Department of Pathology and Laboratory Medicine, University of Vermont, Colchester, VT, USA., Durda P; Department of Pathology and Laboratory Medicine, University of Vermont, Colchester, VT, USA., Kasela S; Department of Systems Biology, New York Genome Center, Columbia University, New York, NY, USA., Lappalinen T; Department of Systems Biology, New York Genome Center, Columbia University, New York, NY, USA., Liu Y; Department of Medicine, Cardiology and Neurology, Duke University Medical Center, Durham, NC, USA., Johnson WC; Department of Biostatistics, University of Washington, Seattle, WA, USA., Van Den Berg DJ; Department of Population and Public Health Sciences, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA., Franceschini N; Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Liu S; Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA., Mouton CP; Department of Family Medicine, University of Texas Medical Branch Health, Galveston, TX, USA., Bhatti P; Department of Medicine, School of Population and Public Health, University of British Columbia, Vancouver, BC, CAN, USA., Horvath S; Department of Human Genetics, David Geffen School of Medicine, Gonda Research Center, Los Angeles, CA, USA.; Altos Labs, San Diego, CA, USA., Whitsel EA; Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Irvin MR; Department of Epidemiology, University of Alabama at Birmingham, 912 18th St S, Birmingham, AL, 35233, USA.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Aug 01; Vol. 14 (1), pp. 17757. Date of Electronic Publication: 2024 Aug 01.
DOI: 10.1038/s41598-024-68470-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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