TY - JOUR
T1 - Enhanced resolution profiling in twins reveals differential methylation signatures of Type 2 Diabetes with links to its complications
AU - Christiansen, Colette
AU - Potier, Louis
AU - Martin, Tiphaine C
AU - Villicana Munoz, Sergio
AU - Castillo Fernandez, Juan
AU - Mangino, Massimo
AU - Menni, Cristina
AU - Tsai, Pei-Chien
AU - Campbell, Purdey J
AU - Mullin, Shelby
AU - Ordoñana, Juan R
AU - Monteagudo, Olga
AU - Sachdev, Perminder S.
AU - Mather, Karen A.
AU - Trollor, Julian N.
AU - Pietiläinen, Kirsi H
AU - Ollikainen, Miina
AU - Dalgård, Christine
AU - Kyvik, Kirsten Ohm
AU - Christensen, Kaare
AU - van Dongen, Jenny
AU - Willemsen, Gonneke
AU - Boomsma, Dorret I.
AU - Magnusson, Patrik KE
AU - Pedersen, Nancy L.
AU - Wilson, Scott G.
AU - Grundberg, Elin
AU - Spector, Tim
AU - Bell, Jordana
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024
Y1 - 2024
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85189532796&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2024.105096
DO - 10.1016/j.ebiom.2024.105096
M3 - Article
SN - 2352-3964
VL - 103
JO - EBioMedicine
JF - EBioMedicine
M1 - 105096
ER -
