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Liu, J.* ; Carnero-Montoro, E.* ; van Dongen, J.* ; Lent, S.* ; Nedeljkovic, I.* ; Ligthart, S.* ; Tsai, P.C.* ; Martin, T.C.* ; Mandaviya, P.R.* ; Jansen, R.* ; Peters, M.J.* ; Duijts, L.* ; Jaddoe, V.W.V.* ; Tiemeier, H.* ; Felix, J.F.* ; Willemsen, G.* ; de Geus, E.J.C.* ; Chu, A.Y.* ; Levy, D.* ; Hwang, S.J.* ; Bressler, J.* ; Gondalia, R.* ; Salfati, E.L.* ; Herder, C.* ; Hidalgo, B.A.* ; Tanaka, T.* ; Moore, A.Z.* ; Lemaitre, R.N.* ; Jhun, M.A.* ; Smith, J.A.* ; Sotoodehnia, N.* ; Bandinelli, S.* ; Ferrucci, L.* ; Arnett, D.K.* ; Grallert, H. ; Assimes, T.L.* ; Hou, L.* ; Baccarelli, A.* ; Whitsel, E.A.* ; van Dijk, K.W.* ; Amin, N.* ; Uitterlinden, A.G.* ; Sijbrands, E.J.G.* ; Franco, O.H.* ; Dehghan, A.* ; Spector, T.D.* ; Dupuis, J.* ; Hivert, M.F.* ; Rotter, J.I.* ; Meigs, J.B.* ; Pankow, J.S.* ; van Meurs, J.B.J.* ; Isaacs, A.* ; Boomsma, D.I.* ; Bell, J.T.* ; Demirkan, A.* ; van Duijn, C.M.*

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

Nat. Commun. 10:2581 (2019)

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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.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Epigenome-wide Association; Body-mass Index; Waist Circumference; Diabetes-mellitus; Fasting Glucose; Glycemic Traits; Up-regulation; Type-2; Gene; Expression

ISSN (print) / ISBN 2041-1723

e-ISSN 2041-1723

Journal Nature Communications

Quellenangaben Volume: 10, Issue: 1, Article Number: 2581

Publisher Nature Publishing Group

Publishing Place London

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Epidemiology II (EPI2)