1. Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.
- Author
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Christiansen C, Potier L, Martin TC, Villicaña S, Castillo-Fernandez JE, Mangino M, Menni C, Tsai PC, Campbell PJ, Mullin S, Ordoñana JR, Monteagudo O, Sachdev PS, Mather KA, Trollor JN, Pietilainen KH, Ollikainen M, Dalgård C, Kyvik K, Christensen K, van Dongen J, Willemsen G, Boomsma DI, Magnusson PKE, Pedersen NL, Wilson SG, Grundberg E, Spector TD, and Bell JT
- Subjects
- Humans, Female, Male, Genome-Wide Association Study, Genetic Predisposition to Disease, Middle Aged, Epigenesis, Genetic, Otx Transcription Factors genetics, Otx Transcription Factors metabolism, Diabetes Complications genetics, Gene Expression Profiling, Diabetes Mellitus, Type 2 genetics, DNA Methylation, CpG Islands
- Abstract
Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and environmental factors. Previous findings suggest DNA methylation as a potential mechanism in T2D pathogenesis and progression., Methods: We profiled DNA methylation in 248 blood samples from participants of European ancestry from 7 twin cohorts using a methylation sequencing platform targeting regulatory genomic regions encompassing 2,048,698 CpG sites., Findings: We find and replicate 3 previously unreported T2D differentially methylated CpG positions (T2D-DMPs) at FDR 5% in RGL3, NGB and OTX2, and 20 signals at FDR 25%, of which 14 replicated. Integrating genetic variation and T2D-discordant monozygotic twin analyses, we identify both genetic-based and genetic-independent T2D-DMPs. The signals annotate to genes with established GWAS and EWAS links to T2D and its complications, including blood pressure (RGL3) and eye disease (OTX2)., Interpretation: The results help to improve our understanding of T2D disease pathogenesis and progression and may provide biomarkers for its complications., Funding: Funding acknowledgements for each cohort can be found in the Supplementary Note., Competing Interests: Declaration of interests The authors have no conflicts to declare., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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