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Lookup NU author(s): Dr Fei Gao, Dr Ana ViñuelaORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© 2014 Macmillan Publishers Limited.DNA methylation has a great potential for understanding the aetiology of common complex traits such as Type 2 diabetes (T2D). Here we perform genome-wide methylated DNA immunoprecipitation sequencing (MeDIP-seq) in whole-blood-derived DNA from 27 monozygotic twin pairs and follow up results with replication and integrated omics analyses. We identify predominately hypermethylated T2D-related differentially methylated regions (DMRs) and replicate the top signals in 42 unrelated T2D cases and 221 controls. The strongest signal is in the promoter of the MALT1 gene, involved in insulin and glycaemic pathways, and related to taurocholate levels in blood. Integrating the DNA methylome findings with T2D GWAS meta-analysis results reveals a strong enrichment for DMRs in T2D-susceptibility loci. We also detect signals specific to T2D-discordant twins in the GPR61 and PRKCB genes. These replicated T2D associations reflect both likely causal and consequential pathways of the disease. The analysis indicates how an integrated genomics and epigenomics approach, utilizing an MZ twin design, can provide pathogenic insights as well as potential drug targets and biomarkers for T2D and other complex traits.
Author(s): Yuan W, Xia Y, Bell CG, Yet I, Ferreira T, Ward KJ, Gao F, Loomis AK, Hyde CL, Wu H, Lu H, Liu Y, Small KS, Vinuela A, Morris AP, Berdasco M, Esteller M, Brosnan MJ, Deloukas P, McCarthy MI, John SL, Bell JT, Wang J, Spector TD
Publication type: Article
Publication status: Published
Journal: Nature Communications
Year: 2014
Volume: 5
Online publication date: 12/12/2014
Acceptance date: 31/10/2014
Date deposited: 19/06/2020
ISSN (electronic): 2041-1723
Publisher: Nature Publishing Group
URL: https://doi.org/10.1038/ncomms6719
DOI: 10.1038/ncomms6719
PubMed id: 25502755
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