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An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins

ABSTRACT: An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins

PROVIDER: PRJEB7663 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR665007_1.fastq.gz	Fastqsanger.gz
	ERR665007_2.fastq.gz	Fastqsanger.gz
	ERR665008_1.fastq.gz	Fastqsanger.gz
	ERR665008_2.fastq.gz	Fastqsanger.gz
	ERR665009_1.fastq.gz	Fastqsanger.gz

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An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins

Project description:The methylation profile for 54 MZ twins are generated by methylated DNA immunoprecipitation followed by sequencing on Illumina GAII. Methylation score (RPM and AMS) is quantified using MEDIPS and differentially methylation region in T2D is detected a linear mixed effect model and MZ discordant twin model.

2014-12-31 | E-MTAB-3051 | biostudies-arrayexpress

An integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins.

Project description: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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Methylomic Analysis reveals Epigenetic Pattern of SH2B1 in Chinese Monozygotic Twins Discordant for Autism Spectrum Disorder [Bisulfite-seq]

Project description:Autism spectrum disorder(ASD) is a complex neurodevelopmental disorder. Aberrant DNA methylation has been observed in ASD but the mechanisms remain largely unknown. Here, we employed discordant monozygotic twins to investigate the contribution of DNA methylation to ASD etiology. Genome-wide DNA methylation analysis was performed using samples obtained from five pairs of ASD-discordant monozygotic twins, which revealed a total of 2397 differentially methylated genes. Further, such gene list was annotated with Kyoto Encyclopedia of Genes and Genomes and demonstrated predominant activation of neurotrophin signaling pathway in ASD-discordant monozygotic twins. The methylation of SH2B1 gene was further confirmed in the ASD-discordant, ASD-concordant monozygotic twins, and a set of 30 pairs of sporadic case-control by bisulfite-pyrosequencing. The results showed that there was a greater DNA methylation difference in ASD-discordant monozygotic twins than ASD-concordant monozygotic twins. Further, verification of the Chr.16:28856743 of SH2B1 showed significant differences in DNA methylation between case and control. These results suggest abnormal methylation of SH2B1 is associated with ASD etiology. Our data suggest that it might be worthwhile to further explore the functions of SH2B1 and related genes of neurotrophin signaling pathway in ASD.

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