An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis.

Liu, Jun; Carnero-Montoro, Elena; van Dongen, Jenny; Lent, Samantha; Nedeljkovic, Ivana; Ligthart, Symen; Tsai, Pei-Chien; Martin, Tiphaine C; Mandaviya, Pooja R; Jansen, Rick; Peters, Marjolein J; Duijts, Liesbeth; Jaddoe, Vincent W V; Tiemeier, Henning; Felix, Janine F; Willemsen, Gonneke; de Geus, Eco J C; Chu, Audrey Y; Levy, Daniel; Hwang, Shih-Jen; ... (2019). An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis. Nature communications, 10(1), p. 2581. Nature Publishing Group 10.1038/s41467-019-10487-4

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Despite existing reports on differential DNA methylation in type 2 diabetes (T2D) and obesity, our understanding of its functional relevance remains limited. Here we show the effect of differential methylation in the early phases of T2D pathology by a blood-based epigenome-wide association study of 4808 non-diabetic Europeans in the discovery phase and 11,750 individuals in the replication. We identify CpGs in LETM1, RBM20, IRS2, MAN2A2 and the 1q25.3 region associated with fasting insulin, and in FCRL6, SLAMF1, APOBEC3H and the 15q26.1 region with fasting glucose. In silico cross-omics analyses highlight the role of differential methylation in the crosstalk between the adaptive immune system and glucose homeostasis. The differential methylation explains at least 16.9% of the association between obesity and insulin. Our study sheds light on the biological interactions between genetic variants driving differential methylation and gene expression in the early pathogenesis of T2D.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine

UniBE Contributor:

Franco Duran, Oscar Horacio

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Andrea Flükiger-Flückiger

Date Deposited:

25 Jun 2019 09:38

Last Modified:

16 Jul 2019 15:56

Publisher DOI:

10.1038/s41467-019-10487-4

PubMed ID:

31197173

BORIS DOI:

10.7892/boris.131440

URI:

https://boris.unibe.ch/id/eprint/131440

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