DNA methylation of blood cells is associated with prevalent type 2 diabetes in a meta-analysis of four European cohorts

Clinical Epigenetics

Tom C. Russ¹  Riccardo E. Marioni²  Trudy Voortman³  Carolina Ochoa-Rosales⁴  Joyce B. J. van Meurs⁵  Marie-France Hivert⁶  Ian J. Deary⁷  Gemma C. Sharp⁸  Hannah R. Elliott⁸  Caroline L. Relton⁹  Diana L. Juvinao-Quintero^1,10 

[1] Alzheimer Scotland Dementia Research Centre, University of Edinburgh, 7 George Square, EH8 9JZ, Edinburgh, UK;Edinburgh Dementia Prevention Research Group, University of Edinburgh, EH16 4UX, Edinburgh, UK;Lothian Birth Cohorts, University of Edinburgh, EH8 9JZ, Edinburgh, UK;Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, EH4 2XU, Edinburgh, UK;Department of Epidemiology, Erasmus MC University Medical Center, 3000 CA, Rotterdam, The Netherlands;Department of Epidemiology, Erasmus MC University Medical Center, 3000 CA, Rotterdam, The Netherlands;Centro de Vida Saludable de La Universidad de Concepción, Victoria 580, Concepción, Chile;Department of Internal Medicine, Erasmus MC University Medical Center, 3000 CA, Rotterdam, The Netherlands;Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care, 02215, Boston, MA, USA;Lothian Birth Cohorts, University of Edinburgh, EH8 9JZ, Edinburgh, UK;Department of Psychology, University of Edinburgh, EH8 9JZ, Edinburgh, UK;MRC Integrative Epidemiology, Bristol Medical School, BS8 2BN, Bristol, UK;Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2BN, Bristol, UK;MRC Integrative Epidemiology, Bristol Medical School, BS8 2BN, Bristol, UK;Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2BN, Bristol, UK;Bristol NIHR Biomedical Research Centre, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, UK;MRC Integrative Epidemiology, Bristol Medical School, BS8 2BN, Bristol, UK;Population Health Sciences, Bristol Medical School, University of Bristol, BS8 2BN, Bristol, UK;Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care, 02215, Boston, MA, USA;MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, BS8 2BN, Bristol, UK;

关键词: DNA methylation;    Prevalent T2D;    Meta-analysis;    ALSPAC;    Europeans;   

DOI  :  10.1186/s13148-021-01027-3

来源: Springer

【 摘 要 】

BackgroundType 2 diabetes (T2D) is a heterogeneous disease with well-known genetic and environmental risk factors contributing to its prevalence. Epigenetic mechanisms related to changes in DNA methylation (DNAm), may also contribute to T2D risk, but larger studies are required to discover novel markers, and to confirm existing ones.ResultsWe performed a large meta-analysis of individual epigenome-wide association studies (EWAS) of prevalent T2D conducted in four European studies using peripheral blood DNAm. Analysis of differentially methylated regions (DMR) was also undertaken, based on the meta-analysis results. We found three novel CpGs associated with prevalent T2D in Europeans at cg00144180 (HDAC4), cg16765088 (near SYNM) and cg24704287 (near MIR23A) and confirmed three CpGs previously identified (mapping to TXNIP, ABCG1 and CPT1A). We also identified 77 T2D associated DMRs, most of them hypomethylated in T2D cases versus controls. In adjusted regressions among diabetic-free participants in ALSPAC, we found that all six CpGs identified in the meta-EWAS were associated with white cell-types. We estimated that these six CpGs captured 11% of the variation in T2D, which was similar to the variation explained by the model including only the common risk factors of BMI, sex, age and smoking (R2 = 10.6%).ConclusionsThis study identifies novel loci associated with T2D in Europeans. We also demonstrate associations of the same loci with other traits. Future studies should investigate if our findings are generalizable in non-European populations, and potential roles of these epigenetic markers in T2D etiology or in determining long term consequences of T2D.

【 授权许可】

CC BY