@article{b1b3872439a0411a8616a37e6c76fe66,
title = "Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications",
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.",
keywords = "DNA methylation, Genetics, Twins, Type 2 diabetes, Genome-Wide Association Study, Genetic Predisposition to Disease, Humans, Middle Aged, Epigenesis, Genetic, Male, Gene Expression Profiling, DNA Methylation, Diabetes Mellitus, Type 2/genetics, Diabetes Complications/genetics, CpG Islands, Female, Otx Transcription Factors/genetics",
author = "Colette Christiansen and Louis Potier and Martin, {Tiphaine C.} and Sergio Villica{\~n}a and Castillo-Fernandez, {Juan E.} and Massimo Mangino and Cristina Menni and Tsai, {Pei Chien} and Campbell, {Purdey J.} and Shelby Mullin and Ordo{\~n}ana, {Juan R.} and Olga Monteagudo and Sachdev, {Perminder S.} and Mather, {Karen A.} and Trollor, {Julian N.} and Pietilainen, {Kirsi H.} and Miina Ollikainen and Christine Dalg{\aa}rd and Kirsten Kyvik and Kaare Christensen and {van Dongen}, Jenny and Gonneke Willemsen and Boomsma, {Dorret I.} and Magnusson, {Patrik K.E.} and Pedersen, {Nancy L.} and Wilson, {Scott G.} and Elin Grundberg and Spector, {Tim D.} and Bell, {Jordana T.}",
note = "Copyright {\textcopyright} 2024 The Author(s). Published by Elsevier B.V. All rights reserved.",
year = "2024",
month = may,
doi = "10.1016/j.ebiom.2024.105096",
language = "英语",
volume = "103",
pages = "105096",
journal = "EBioMedicine",
issn = "2352-3964",
publisher = "Elsevier B.V.",
}
