Epigenome-wide association study of kidney function identifies trans-ethnic and ethnic-specific loci.

Autor:	Breeze CE; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, MD, USA. c.breeze@ucl.ac.uk.; UCL Cancer Institute, University College London, London, WC1E 6BT, UK. c.breeze@ucl.ac.uk.; Altius Institute for Biomedical Sciences, Seattle, WA, 98121, USA. c.breeze@ucl.ac.uk., Batorsky A; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, 27516, USA., Lee MK; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, 27709, USA., Szeto MD; Division of Biomedical Informatics and Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Xu X; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., McCartney DL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK., Jiang R; Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC, 27701, USA., Patki A; Department of Biostatistics, University of Alabama, Birmingham, AL, USA., Kramer HJ; Department of Public Health Sciences and Medicine, Loyola University Chicago, Maywood, IL, USA.; Division of Nephrology and Hypertension, Loyola University Chicago, Maywood, IL, USA., Eales JM; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Raffield L; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA., Lange L; Division of Biomedical Informatics and Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Lange E; Division of Biomedical Informatics and Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA., Durda P; Department of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA., Liu Y; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA., Tracy RP; Department of Pathology & Laboratory Medicine, Larner College of Medicine, University of Vermont, Burlington, VT, USA.; Department of Biochemistry, Larner College of Medicine, University of Vermont, Burlington, VT, USA., Van Den Berg D; Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA., Evans KL; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK., Kraus WE; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.; Division of Cardiology, Department of Medicine, School of Medicine, Duke University, Durham, NC, USA., Shah S; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.; Division of Cardiology, Department of Medicine, School of Medicine, Duke University, Durham, NC, USA., Tiwari HK; Department of Biostatistics, University of Alabama, Birmingham, AL, USA., Hou L; Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.; Center for Global Oncology, Institute of Global Health, Northwestern University Feinberg School of Medicine, Chicago, IL, USA., Whitsel EA; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA.; Department of Medicine, University of North Carolina, Chapel Hill, NC, 27599, USA., Jiang X; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK., Charchar FJ; School of Health and Life Sciences, Federation University Australia, Ballarat, VIC, Australia.; Department of Physiology, University of Melbourne, Parkville, VIC, Australia.; Department of Cardiovascular Sciences, University of Leicester, Leicester, UK., Baccarelli AA; Laboratory of Environmental Epigenetics, Departments of Environmental Health Sciences and Epidemiology, Columbia University Mailman School of Public Health, New York, NY, USA., Rich SS; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Morris AP; Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK., Irvin MR; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA., Arnett DK; College of Public Health, University of Kentucky, Lexington, KY, USA., Hauser ER; Duke Molecular Physiology Institute, Duke University Medical Center, Durham, NC, USA.; Durham VA Health System, Durham, NC, 27705, 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., Correa A; Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA., Hayward C; MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK., Horvath S; Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, 90095, USA.; Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA, 90095, USA., Marioni RE; Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Crewe Road, Edinburgh, EH4 2XU, UK., Tomaszewski M; Division of Cardiovascular Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.; Manchester Heart Centre and Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Manchester, UK., Beck S; UCL Cancer Institute, University College London, London, WC1E 6BT, UK., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department Health and Human Services, Bethesda, MD, USA., London SJ; Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC, 27709, USA., Mychaleckyj JC; Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA., Franceschini N; Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA. noraf@unc.edu.
Jazyk:	angličtina
Zdroj:	Genome medicine [Genome Med] 2021 Apr 30; Vol. 13 (1), pp. 74. Date of Electronic Publication: 2021 Apr 30.
DOI:	10.1186/s13073-021-00877-z
Abstrakt:	Background: DNA methylation (DNAm) is associated with gene regulation and estimated glomerular filtration rate (eGFR), a measure of kidney function. Decreased eGFR is more common among US Hispanics and African Americans. The causes for this are poorly understood. We aimed to identify trans-ethnic and ethnic-specific differentially methylated positions (DMPs) associated with eGFR using an agnostic, genome-wide approach. Methods: The study included up to 5428 participants from multi-ethnic studies for discovery and 8109 participants for replication. We tested the associations between whole blood DNAm and eGFR using beta values from Illumina 450K or EPIC arrays. Ethnicity-stratified analyses were performed using linear mixed models adjusting for age, sex, smoking, and study-specific and technical variables. Summary results were meta-analyzed within and across ethnicities. Findings were assessed using integrative epigenomics methods and pathway analyses. Results: We identified 93 DMPs associated with eGFR at an FDR of 0.05 and replicated 13 and 1 DMPs across independent samples in trans-ethnic and African American meta-analyses, respectively. The study also validated 6 previously published DMPs. Identified DMPs showed significant overlap enrichment with DNase I hypersensitive sites in kidney tissue, sites associated with the expression of proximal genes, and transcription factor motifs and pathways associated with kidney tissue and kidney development. Conclusions: We uncovered trans-ethnic and ethnic-specific DMPs associated with eGFR, including DMPs enriched in regulatory elements in kidney tissue and pathways related to kidney development. These findings shed light on epigenetic mechanisms associated with kidney function, bridging the gap between population-specific eGFR-associated DNAm and tissue-specific regulatory context.
Databáze:	MEDLINE
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