RT Journal Article
T1 An integrative cross-omics analysis of DNA methylation sites of glucose and insulin homeostasis.
A1 Liu, Jun
A1 Carnero-Montoro, Elena
A1 van Dongen, Jenny
A1 Lent, Samantha
A1 Nedeljkovic, Ivana
A1 Ligthart, Symen
A1 Tsai, Pei-Chien
A1 Martin, Tiphaine C
A1 Mandaviya, Pooja R
A1 Jansen, Rick
A1 Peters, Marjolein J
A1 Duijts, Liesbeth
A1 Jaddoe, Vincent W V
A1 Tiemeier, Henning
A1 Felix, Janine F
A1 Willemsen, Gonneke
A1 de Geus, Eco J C
A1 Chu, Audrey Y
A1 Levy, Daniel
A1 Hwang, Shih-Jen
A1 Bressler, Jan
A1 Gondalia, Rahul
A1 Salfati, Elias L
A1 Herder, Christian
A1 Hidalgo, Bertha A
A1 Tanaka, Toshiko
A1 Moore, Ann Zenobia
A1 Lemaitre, Rozenn N
A1 Jhun, Min A
A1 Smith, Jennifer A
A1 Sotoodehnia, Nona
A1 Bandinelli, Stefania
A1 Ferrucci, Luigi
A1 Arnett, Donna K
A1 Grallert, Harald
A1 Assimes, Themistocles L
A1 Hou, Lifang
A1 Baccarelli, Andrea
A1 Whitsel, Eric A
A1 van Dijk, Ko Willems
A1 Amin, Najaf
A1 Uitterlinden, André G
A1 Sijbrands, Eric J G
A1 Franco, Oscar H
A1 Dehghan, Abbas
A1 Spector, Tim D
A1 Dupuis, Josée
A1 Hivert, Marie-France
A1 Rotter, Jerome I
A1 Meigs, James B
A1 Pankow, James S
A1 van Meurs, Joyce B J
A1 Isaacs, Aaron
A1 Boomsma, Dorret I
A1 Bell, Jordana T
A1 Demirkan, Ayşe
A1 van Duijn, Cornelia M
AB 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.
YR 2019
FD 2019-06-13
LK http://hdl.handle.net/10668/14112
UL http://hdl.handle.net/10668/14112
LA en
DS RISalud
RD Apr 10, 2025