An Integrated Epigenomic Analysis for Type 2 Diabetes Susceptibility Loci in Monozygotic Twins

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Dec 16

PMID 25502755

Citations 55

Authors

Wei Yuan

Yudong Xia

Christopher G Bell

Idil Yet

Teresa Ferreira

Kirsten J Ward

Fei Gao

A Katrina Loomis

Craig L Hyde

Honglong Wu

Hanlin Lu

Yuan Liu

Kerrin S Small

Ana Vinuela

Andrew P Morris

Maria Berdasco

Manel Esteller

M Julia Brosnan

Panos Deloukas

Mark I McCarthy

Sally L John

Jordana T Bell

Jun Wang

Tim D Spector

Affiliations

Soon will be listed here.

Abstract

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.

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