Dataset Information

Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice.

ABSTRACT: Heritable epigenetic factors can contribute to complex disease etiology. Here we examine the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes, and osteoporosis. We profiled DNA methylation in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics, and 68 clinical traits and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical traits including bone density, insulin resistance, expression, and protein and metabolite levels. A large proportion of associations were unique to EWAS and were not identified using GWAS. Methylation levels were regulated by genetics largely in cis, but we also found evidence of trans regulation, and we demonstrate that genetic variation in the methionine synthase reductase gene Mtrr affects methylation of hundreds of CpGs throughout the genome. Our results indicate that natural variation in methylation levels contributes to the etiology of complex clinical traits.

SUBMITTER: Orozco LD

PROVIDER: S-EPMC4454894 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice.

Orozco Luz D LD Morselli Marco M Rubbi Liudmilla L Guo Weilong W Go James J Shi Huwenbo H Lopez David D Furlotte Nicholas A NA Bennett Brian J BJ Farber Charles R CR Ghazalpour Anatole A Zhang Michael Q MQ Bahous Renata R Rozen Rima R Lusis Aldons J AJ Pellegrini Matteo M

Cell metabolism 20150601 6

Heritable epigenetic factors can contribute to complex disease etiology. Here we examine the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes, and osteoporosis. We profiled DNA methylation in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics, and 68 clinical traits and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical traits includ ...[more]

PMID: 26039453

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Project description:Epigenetic changes are important for understanding complex trait variation and inheritance in pigs that are also a valuable biomedical model for human health research. Testis is the main organ for reproduction and boar taint in pigs; however, there have been no studies to-date on adult pig testis epigenome. The main objective of this study was to establish a genome-wide DNA methylation map of pig testis that would help identify candidate epigenetic biomarkers and methylated genes for complex traits such as male reproduction, fertility or boar taint. Reduced Representation Bisulfite Sequencing (RRBS) was used to study methylation levels of cytosine in nine pig testis samples. The results showed that genome-wide methylation status of nine samples overlapped greatly and their variation among pigs were low. The methylation levels of promoter, exon, intron, cytosine and guanine dinucleotide (CpG) islands and CpG island shores regions were 0.15, 0.47, 0.55, 0.39, and 0.53, respectively. Cytosines binding to CpG islands showed different methylation levels between exon and intron regions. All methylation levels of CpG islands were lower than CpG island shores in different genic features. The distribution of 12,738 differentially methylated cytosines (DMCs) within CpG islands, CpG island shores and other regions was 36.86, 21.65, and 41.49%, respectively, and was 0.33, 1.71, 5.95, and 92.01% in promoter, exon, intron and intergenic regions, respectively. Methylation levels of DMCs in promoter, exon and intron regions were significantly different between CpG islands and CpG island shores (P < 0.05). A total of 898 genes with 2089 DMCs were enriched in 112 Gene Ontology (GO) terms. Fifteen methylated genes from our study were associated with fertility or boar taint traits. Our analysis revealed the methylation patterns in different genic features and CpG island regions of testis in pigs, and summarized several candidate genes associated with DMCs and the involved GO terms. These findings are helpful to understand the relationship between DNA methylation and genic CpG islands, to provide candidate epigenetic regions or biomarkers for pig production and welfare and for translational epigenomic studies that use pigs as an animal model for human research.

Dataset Information

Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice.

Publications

Epigenome-wide association of liver methylation patterns and complex metabolic traits in mice.

Similar Datasets

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