Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA280119 | ENA |
REPOSITORIES: ENA
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Project description:Heritable epigenetic factors can contribute to complex disease etiology. In this study we examine, on a global scale, the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes and osteoporosis. We profiled DNA methylation patterns in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics and sixty-eight clinical traits, and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical traits including bone mineral density, plasma cholesterol, insulin resistance, gene expression, 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. Reduced representation bisulfite sequencing in mouse strains using liver genomic DNA
2015-04-02 | E-GEOD-67507 | biostudies-arrayexpress
Project description:Heritable epigenetic factors can contribute to complex disease etiology. In this study we examine, on a global scale, the contribution of DNA methylation to complex traits that are precursors to heart disease, diabetes and osteoporosis. We profiled DNA methylation patterns in the liver using bisulfite sequencing in 90 mouse inbred strains, genome-wide expression levels, proteomics, metabolomics and sixty-eight clinical traits, and performed epigenome-wide association studies (EWAS). We found associations with numerous clinical traits including bone mineral density, plasma cholesterol, insulin resistance, gene expression, 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.
2015-04-02 | GSE67507 | GEO
Project description:In this study, we examined the association of DNA methylation with metabolic traits in humans using adipose tissue samples from the Metabolic Syndrome in Men (METSIM) cohort. The METSIM cohort has been thoroughly characterized for longitudinal clinical data of metabolic traits including a 3-point oral glucose tolerance test, cardiovascular disorders, diabetes complications, drug and diet questionnaire, as well as high density genotyping, and genome-wide expression in adipose. We performed epigenome-wide association studies on clinical traits using reduced representation bisulfite sequencing data and identified 61 signifiant associations for metabolic syndrome traits, corresponding to 25 unique loci. These associations include previously known genes, FASN, RXRA, MSH2, and MSH6, as well as 22 loci harboring 18 new candidate genes for diabetes and obesity in humans.
2017-01-01 | GSE87893 | GEO
Project description:Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The non-inbred mouse (Mus musculus) line Titan, also known as DU6, is one of the world’s longest selection experiments for high body mass and was previously described as a model for metabolic healthy (benign) obesity. The present study further characterizes the geno- and phenotypes of this non-inbred mouse line and testes its suitability as an interventional obesity model. In contrast to previous findings, our data suggest that Titan mice are metabolically unhealthy obese and short-lived. Line-specific patterns of genetic invariability are in accordance with observed phenotypic traits. Titan mice also show modifications in the liver transcriptome, proteome, and epigenome linked to metabolic (dys)regulations. Importantly, dietary intervention partially reversed the metabolic phenotype in Titan mice and significantly extended their life expectancy. Therefore, the Titan mouse line is a valuable resource for translational and interventional obesity research
2022-05-04 | PXD019030 | Pride
Project description:Suitable animal models are essential for translational research, especially in the case of complex, multifactorial conditions, such as obesity. The non-inbred mouse (Mus musculus) line Titan, also known as DU6, is one of the world’s longest selection experiments for high body mass and was previously described as a model for metabolic healthy (benign) obesity. The present study further characterizes the geno- and phenotypes of this non-inbred mouse line and testes its suitability as an interventional obesity model. In contrast to previous findings, our data suggest that Titan mice are metabolically unhealthy obese and short-lived. Line-specific patterns of genetic invariability are in accordance with observed phenotypic traits. Titan mice also show modifications in the liver transcriptome, proteome, and epigenome linked to metabolic (dys)regulations. Importantly, dietary intervention partially reversed the metabolic phenotype in Titan mice and significantly extended their life expectancy. Therefore, the Titan mouse line is a valuable resource for translational and interventional obesity research.
2022-05-01 | GSE150073 | GEO
Project description:Epigenome-wide association in the METSIM cohort identifies 22 novel loci for diabetes and metabolic syndrome traits
| PRJNA348122 | ENA
Project description:Studies on aging have largely included one or two OMICS layers, which may not necessarily reflect the signatures of other layers. Moreover, most aging studies have often compared very young (4-5 wks) mice with old (24 months) mice which does not reflect the aging transition after the attainment of adulthood. Therefore, we aimed to study and compared muti-OMICS aging signatures across key metabolic tissues of mature adults (6 months) and old (24 months) C57BL/6J mice (the most commonly used mouse strain). Here we compared the differentially regulated genes and enriched pathways for transcriptome, proteome and epigenome (H3K27ac, H3K4me3, H3K27me3, DNA methylation) across liver, heart, and quadriceps muscle. The major aging associated pathways cross multiple layers and tissues are decreased RNA metabolism, transcription, and translation at transcript and protein levels however increased potential of transcription at DNA methylation and H3K27ac levels.
2021-11-30 | PXD011142 | Pride
Project description:A major task in dissecting the genetics of complex traits is to identify causal genes for disease phenotypes. We previously developed a method to infer causal relationships among genes through the integration of DNA variation, gene transcription, and phenotypic information. Here we validated our method through the characterization of transgenic and knockout mouse models of candidate genes that were predicted to be causal for abdominal obesity. Perturbation of eight out of the nine genes, with Gas7, Me1 and Gpx3 being novel, resulted in significant changes in obesity related traits. Liver expression signatures revealed alterations in common metabolic pathways and networks contributing to abdominal obesity and overlapped with a macrophage-enriched metabolic network module that is highly associated with metabolic traits in mice and humans. Integration of gene expression in the design and analysis of traditional F2 intercross studies allows high confidence prediction of causal genes, and identification of involved pathways and networks. This SuperSeries is composed of the following subset Series: GSE11991: Liver gene expression profiling of lipoprotein lipase heterozygous knockout mice GSE11992: Liver gene expression profiling of cytosolic malic enzyme knockout mice GSE11993: Liver gene expression profiling of zinc finger binding protein 90 (Zfp90) transgenic mice GSE11994: Liver gene expression profiling of transforming growth factor beta receptor 2 heterozygous knockout (Tgfbr2+/-) mice GSE11995: Liver gene expression profiling of complement component 3a receptor 1 knockout (C3ar1-/-) mice GSE11996: Gas7 male transgenic liver expression vs FVB male wildtype control GSE11997: Gpx3 male transgenic liver expression vs B6/DBA male wildtype control GSE11998: Gyk female heterozygous liver expression vs C57Bl/6J female wildtype control GSE11999: Lactb male transgenic liver expression vs FVB male wildtype control Refer to individual Series
2009-03-07 | E-GEOD-12000 | biostudies-arrayexpress
Project description:Association of cord blood methylation with neonatal leptin: an epigenome wide association study
| PRJNA532930 | ENA
Project description:An epigenome-wide association study (EWAS) was performed on buccal cells from monozygotic-twins (MZ) reared together as children, but who live apart as adults. Cohorts of twin pairs were used to investigate associations between neighborhood walkability and objectively measured physical activity (PA) levels. Due to dramatic cellular epigenetic sex differences, male and female MZ twin pairs were analyzed separately to identify differential DNA methylation regions (DMRs). A priori comparisons were made on MZ twin pairs discordant on body mass index (BMI), PA levels, and neighborhood walkability. In addition to direct comparative analysis to identify specific DMRs, a weighted gene coexpression network analysis (WGCNA) was performed to identify DNA methylation sites associated with the physiological traits of interest. The pairs discordant in PA levels had epigenetic alterations that correlated with reduced metabolic parameters (i.e., BMI). The DNA methylation sites are associated with over fifty genes previously found to be specific to vigorous PA, metabolic risk factors, and sex. Combined observations demonstrate that behavioral factors, such as physical activity, appear to promote systemic epigenetic alterations that impact metabolic risk factors. The epigenetic DNA methylation sites and associated genes identified provide insight into PA impacts on metabolic parameters and the etiology of obesity.
2022-12-01 | GSE216387 | GEO