The effect of genotype and in utero environment on inter-individual variation in neonate DNA methylomes
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE54446 | GEO | 2014/04/02
SECONDARY ACCESSION(S): PRJNA236530
REPOSITORIES: GEO
Similar Datasets
Project description:We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. Although methQTLs were readily detected in neonatal methylomes, genotype alone did not explain the majority of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age and birth order.
2014-04-02 | GSE53816 | GEO
Project description:We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. Although methQTLs were readily detected in neonatal methylomes, genotype alone did not explain the majority of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age and birth order. We surveyed the genotypes and DNA methylomes of 237 neonates and included 32 technical replicates
2014-04-02 | E-GEOD-53816 | biostudies-arrayexpress
Project description:We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. Although methQTLs were readily detected in neonatal methylomes, genotype alone did not explain the majority of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age and birth order. We surveyed the genotypes and DNA methylomes of 237 neonates
2014-04-02 | E-GEOD-54445 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2014-04-02 | E-GEOD-54446 | biostudies-arrayexpress
Project description:We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. Although methQTLs were readily detected in neonatal methylomes, genotype alone did not explain the majority of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age and birth order.
2014-04-02 | GSE54445 | GEO
Project description:Integrating the genotype with epigenetic marks holds the promise of better understanding the biology that underlies the complex interactions of inherited and environmental components that define the developmental origins of a range of disorders. The quality of the in utero environment significantly influences health over the lifecourse. Epigenetics, and in particular DNA methylation marks, have been postulated as a mechanism for the enduring effects of the prenatal environment. Accordingly, neonate methylomes contain molecular memory of the individual in utero experience. However, interindividual variation in methylation can also be a consequence of DNA sequence polymorphisms that result in methylation quantitative trait loci (methQTLs) and, potentially, the interaction between fixed genetic variation and environmental influences. We surveyed the genotypes and DNA methylomes of 237 neonates and found 1423 punctuate regions of the methylome that were highly variable across individuals, termed variably methylated regions (VMRs), against a backdrop of homogeneity. MethQTLs were readily detected in neonatal methylomes, and genotype alone best explained ∼25% of the VMRs. We found that the best explanation for 75% of VMRs was the interaction of genotype with different in utero environments, including maternal smoking, maternal depression, maternal BMI, infant birth weight, gestational age, and birth order. Our study sheds new light on the complex relationship between biological inheritance as represented by genotype and individual prenatal experience and suggests the importance of considering both fixed genetic variation and environmental factors in interpreting epigenetic variation.
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Project description:Isogenic individuals growing in the same environment often show substantial phenotypic variation. The causes, consequences and molecular bases of inter-individual variation are usually poorly understood. To characterize molecular differences between isogenic individuals, we measured genome-wide expression profiles in synchronized single young adult C. elegans worms.
2017-12-05 | GSE98747 | GEO
Project description:Study hypothesis: CRC risk is affected by diet and by genetic polymorphisms leading to inter-individual variation in the metabolism of environmental carcinogens. Our first hypothesis is that these effects may combine to place certain individuals at greatly enhanced risk according to their diet. We shall examine how dietary factors known to affect CRC risk (including meats, fat, fruit and vegetables, cooking methods, dietary supplements and drugs) and genetic polymorphisms implicated in CRC (Glutathione S-transferase: GSTM1, GSTM3, GSTT1; N-acetyl transferase: NAT1, NAT2; and Cytochrome P450: CYP1A1, CYP2D6) combine to affect the prevalence of colorectal polyps, both adenomatous (the precursor lesion of CRC) and metaplastic.
Our second hypothesis is that diets associated with increased risk (high red meat, low vegetable and low fibre consumption) may affect DNA damage markers which may be elevated in people with colorectal adenomas.
We shall therefore examine the effect of diet on adduct rates (cross sectional) and adduct rates in people with and without colorectal adenomas. We shall examine malondialdehyde adduct rates in relation to anti-oxidant status and carboxymethyl adduct rates and k-ras mutation frequency in relation to meat consumption; and examine the effect of DNA repair enzyme (ATase) activity on any relationship found. In summary the aim of this population based study is to link dietary factors thought to be important in the genesis of colorectal polyps and cancer with genetic polymorphisms and DNA damage markers in rectal mucosa and in blood.
Primary outcome(s): We shall perform cross-sectional and case-control analyses of the effect of diet and genetic polymorphisms on the prevalence of adenomatous and metaplastic polyps. Genetic polymorphisms will be examined in isolation and paired combinations and in groups stratified according to diet. We shall examine the effect of diet on MDA adduct rates (concentrating on foods relating to anti-oxidant status) and CBM adduct rates and k-ras mutations (concentrating on meat consumption and cooking methods) by categorical variables; and MDA and CBM adducts and k-ras mutation frequency in people with adenomatous polyps and polyp free controls (case-control). We shall examine the affect of ATase activity on any relationship found and ATase activity in people with adenomatous polyps and polyp free controls (case control).
DNA will be stored for future analysis of as yet unrecognised polymorphisms which may be recognised as having a role in CRC. Samples taken from EPIC participants for adduct, ATase and k-ras measurement whose polyps are found to be metaplastic will be stored for possible future analysis: we shall investigate people with adenomatous polyps in the first instance as these are the precursors of colorectal cancer.
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Project description:The aim of this study was to map inter-individual variation in the human milk peptidome and to investigate relationships between these data and possible explanations for observed variation.
2022-05-04 | PXD028294 | Pride
Project description:Genomic DNA methylation profiles exhibit substantial variation within the human population, with important functional implications for gene regulation. So far little is known about the characteristics and determinants of DNA methylation variation among healthy individuals. We performed bioinformatic analysis of high-resolution methylation profiles from multiple individuals, uncovering complex patterns of inter-individual variation that are strongly correlated with the local DNA sequence. CpG-rich regions exhibit low and relatively similar levels of DNA methylation in all individuals, but the sequential order of the (few) methylated among the (many) unmethylated CpGs differs randomly across individuals. In contrast, CpG-poor regions exhibit substantially elevated levels of inter-individual variation, but also significant conservation of specific DNA methylation patterns between unrelated individuals. This observation has important implications for experimental analysis of DNA methylation, e.g. in the context of epigenome projects. First, DNA methylation mapping at single-CpG resolution is expected to uncover informative DNA methylation patterns for the CpG-poor bulk of the human genome. Second, for CpG-rich regions it will be sufficient to measure average methylation levels rather than assaying every single CpG. We substantiate these conclusions by an in silico benchmarking study of six widely used methods for DNA methylation mapping. Based on our findings, we propose a cost-optimized two-track strategy for mammalian methylome projects.
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