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

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2019-06-13

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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

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Abstract

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.

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Adult
Aged
Aged, 80 and over
Computer Simulation
CpG Islands
DNA Methylation
Diabetes Mellitus, Type 2
Epigenesis, Genetic
Epigenomics
Female
Gene Expression Profiling
Gene Expression Regulation
Genome-Wide Association Study
Glucose
Homeostasis
Humans
Insulin
Male
Metabolic Networks and Pathways
Middle Aged
Obesity
Polymorphism, Single Nucleotide
Young Adult

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