Document Type
Article
Publication Date
5-2024
Identifier
DOI: 10.1016/j.ebiom.2024.105096; PMCID: PMC11004697
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.
Journal Title
EBioMedicine
Volume
103
First Page
105096
Last Page
105096
MeSH Keywords
Humans; Diabetes Mellitus, Type 2; DNA Methylation; CpG Islands; Female; Male; Genome-Wide Association Study; Genetic Predisposition to Disease; Middle Aged; Epigenesis, Genetic; Otx Transcription Factors; Diabetes Complications; Gene Expression Profiling
Keywords
DNA methylation; Genetics; Twins; Type 2 diabetes.
Recommended Citation
Christiansen C, Potier L, Martin TC, et al. Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications. EBioMedicine. 2024;103:105096. doi:10.1016/j.ebiom.2024.105096
Comments
This is an open access article distributed under the terms of the Creative Commons CC-BY license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Publisher's Link: https://www.thelancet.com/journals/ebiom/article/PIIS2352-3964(24)00131-2/fulltext