Epigenome-wide meta-analysis identifies DNA methylation biomarkers associated with diabetic kidney disease.

Autor: Smyth LJ; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK., Dahlström EH; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland., Syreeni A; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland., Kerr K; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK., Kilner J; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK., Doyle R; Diabetes Complications Research Centre, Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland., Brennan E; Diabetes Complications Research Centre, Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland., Nair V; Department of Medicine-Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA., Fermin D; Department of Pediatrics-Nephrology, University of Michigan School of Medicine, Ann Arbor, MI, 48109, USA., Nelson RG; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA., Looker HC; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ, USA., Wooster C; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK., Andrews D; Diabetes Complications Research Centre, Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland., Anderson K; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK., McKay GJ; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK., Cole JB; Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA, USA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA., Salem RM; Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA., Conlon PJ; Department of Nephrology and Transplantation, Beaumont Hospital and Department of Medicine Royal College of Surgeons in Ireland, Dublin 9, Ireland., Kretzler M; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA., Hirschhorn JN; Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA, USA.; Division of Endocrinology, Boston Children's Hospital, Boston, MA, USA.; Department of Pediatrics and Genetics, Harvard Medical School, Boston, MA, USA., Sadlier D; Mater Misericordiae Hospital, D07 K201, Dublin, Ireland., Godson C; Diabetes Complications Research Centre, Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland., Florez JC; Programs in Metabolism and Medical & Population Genetics, Broad Institute, Cambridge, MA, USA.; Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA.; Department of Medicine, Harvard Medical School, Boston, MA, USA., Forsblom C; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland., Maxwell AP; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK.; Regional Nephrology Unit, Belfast City Hospital, Belfast, Northern Ireland, UK., Groop PH; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland.; Department of Diabetes, Central Clinical School, Monash University, Melbourne, Victoria, Australia., Sandholm N; Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland. niina.sandholm@helsinki.fi.; Department of Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. niina.sandholm@helsinki.fi.; Research Program for Clinical and Molecular Metabolism, Faculty of Medicine, University of Helsinki, 00290, Helsinki, Finland. niina.sandholm@helsinki.fi., McKnight AJ; Molecular Epidemiology Research Group, Centre for Public Health, Queen's University Belfast, Belfast, UK. a.j.mcknight@qub.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Dec 22; Vol. 13 (1), pp. 7891. Date of Electronic Publication: 2022 Dec 22.
DOI: 10.1038/s41467-022-34963-6
Abstrakt: Type 1 diabetes affects over nine million individuals globally, with approximately 40% developing diabetic kidney disease. Emerging evidence suggests that epigenetic alterations, such as DNA methylation, are involved in diabetic kidney disease. Here we assess differences in blood-derived genome-wide DNA methylation associated with diabetic kidney disease in 1304 carefully characterised individuals with type 1 diabetes and known renal status from two cohorts in the United Kingdom-Republic of Ireland and Finland. In the meta-analysis, we identify 32 differentially methylated CpGs in diabetic kidney disease in type 1 diabetes, 18 of which are located within genes differentially expressed in kidneys or correlated with pathological traits in diabetic kidney disease. We show that methylation at 21 of the 32 CpGs predict the development of kidney failure, extending the knowledge and potentially identifying individuals at greater risk for diabetic kidney disease in type 1 diabetes.
(© 2022. The Author(s).)
Databáze: MEDLINE
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