Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications

Colette Christiansen; Louis Potier; Tiphaine C. Martin; Sergio Villicaña; Juan E. Castillo-Fernandez; Massimo Mangino; Cristina Menni; Pei Chien Tsai; Purdey J. Campbell; Shelby Mullin; Juan R. Ordoñana; Olga Monteagudo; Perminder S. Sachdev; Karen A. Mather; Julian N. Trollor; Kirsi H. Pietilainen; Miina Ollikainen; Christine Dalgård; Kirsten Kyvik; Kaare Christensen; Jenny van Dongen; Gonneke Willemsen; Dorret I. Boomsma; Patrik K.E. Magnusson; Nancy L. Pedersen; Scott G. Wilson; Elin Grundberg; Tim D. Spector; Jordana T. Bell

doi:10.1016/j.ebiom.2024.105096

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications

Colette Christiansen^*, Louis Potier, Tiphaine C. Martin, Sergio Villicaña, Juan E. Castillo-Fernandez, Massimo Mangino, Cristina Menni, Pei Chien Tsai, Purdey J. Campbell, Shelby Mullin, Juan R. Ordoñana, Olga Monteagudo, Perminder S. Sachdev, Karen A. Mather, Julian N. Trollor, Kirsi H. Pietilainen, Miina Ollikainen, Christine Dalgård, Kirsten Kyvik, Kaare ChristensenJenny van Dongen, Gonneke Willemsen, Dorret I. Boomsma, Patrik K.E. Magnusson, Nancy L. Pedersen, Scott G. Wilson, Elin Grundberg, Tim D. Spector, Jordana T. Bell^*

^*Corresponding author for this work

Department of Biomedical Sciences (Master's Program in Clinical Trials Assessment)

Research output: Contribution to journal › Journal Article › peer-review

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.

Original language	English
Article number	105096
Pages (from-to)	105096
Journal	EBioMedicine
Volume	103
DOIs	https://doi.org/10.1016/j.ebiom.2024.105096
State	Published - 05 2024

Bibliographical 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ebiom.2024.105096

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Christiansen, C., Potier, L., Martin, T. C., Villicaña, S., Castillo-Fernandez, J. E., Mangino, M., Menni, C., Tsai, P. C., Campbell, P. J., Mullin, S., Ordoñana, J. R., Monteagudo, O., Sachdev, P. S., Mather, K. A., Trollor, J. N., Pietilainen, K. H., Ollikainen, M., Dalgård, C., Kyvik, K., ... Bell, J. T. (2024). Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications. EBioMedicine, 103, 105096. Article 105096. https://doi.org/10.1016/j.ebiom.2024.105096

@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.}",

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.",

}

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 & Bell, JT 2024, 'Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications', EBioMedicine, vol. 103, 105096, pp. 105096. https://doi.org/10.1016/j.ebiom.2024.105096

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 - Villicaña, Sergio

AU - Castillo-Fernandez, Juan E.

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 - Pietilainen, Kirsi H.

AU - Ollikainen, Miina

AU - Dalgård, Christine

AU - Kyvik, Kirsten

AU - Christensen, Kaare

AU - van Dongen, Jenny

AU - Willemsen, Gonneke

AU - Boomsma, Dorret I.

AU - Magnusson, Patrik K.E.

AU - Pedersen, Nancy L.

AU - Wilson, Scott G.

AU - Grundberg, Elin

AU - Spector, Tim D.

AU - Bell, Jordana T.

PY - 2024/5

Y1 - 2024/5

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.

KW - DNA methylation

KW - Genetics

KW - Twins

KW - Type 2 diabetes

KW - Genome-Wide Association Study

KW - Genetic Predisposition to Disease

KW - Humans

KW - Middle Aged

KW - Epigenesis, Genetic

KW - Male

KW - Gene Expression Profiling

KW - DNA Methylation

KW - Diabetes Mellitus, Type 2/genetics

KW - Diabetes Complications/genetics

KW - CpG Islands

KW - Female

KW - Otx Transcription Factors/genetics

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U2 - 10.1016/j.ebiom.2024.105096

DO - 10.1016/j.ebiom.2024.105096

M3 - 文章

C2 - 38574408

AN - SCOPUS:85189532796

SN - 2352-3964

VL - 103

SP - 105096

JO - EBioMedicine

JF - EBioMedicine

M1 - 105096

ER -

Enhanced resolution profiling in twins reveals differential methylation signatures of type 2 diabetes with links to its complications

Abstract

Bibliographical note

Keywords

UN SDGs

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