Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications.
EBioMedicine
; 103: 105096, 2024 May.
Article
em En
| MEDLINE
| ID: mdl-38574408
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ilhas de CpG
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Metilação de DNA
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Diabetes Mellitus Tipo 2
Limite:
Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
EBioMedicine
Ano de publicação:
2024
Tipo de documento:
Article