Dataset Information

The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.

ABSTRACT: 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.

SUBMITTER: Teh AL

PROVIDER: S-EPMC4079963 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.

Teh Ai Ling AL Pan Hong H Chen Li L Ong Mei-Lyn ML Dogra Shaillay S Wong Johnny J MacIsaac Julia L JL Mah Sarah M SM McEwen Lisa M LM Saw Seang-Mei SM Godfrey Keith M KM Chong Yap-Seng YS Kwek Kenneth K Kwoh Chee-Keong CK Soh Shu-E SE Chong Mary F F MF Barton Sheila S Karnani Neerja N Cheong Clara Y CY Buschdorf Jan Paul JP Stünkel Walter W Kobor Michael S MS Meaney Michael J MJ Gluckman Peter D PD Holbrook Joanna D JD

Genome research 20140407 7

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, neon ...[more]

PMID: 24709820

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Project description:Peripheral blood monocytes (PBMs) play multiple and critical roles in the immune response, and abnormalities in PBMs have been linked to a variety of human disorders. However, the DNA methylation landscape in PBMs is largely unknown. In this study, we characterized epigenome-wide DNA methylation profiles in purified PBMs.PBMs were isolated from freshly collected peripheral blood from 18 unrelated healthy postmenopausal Caucasian females. Epigenome-wide DNA methylation profiles (the methylome) were characterized by using methylated DNA immunoprecipitation combined with high-throughput sequencing.Distinct patterns were revealed at different genomic features. For instance, promoters were commonly (?58%) found to be unmethylated; whereas protein coding regions were largely (?84%) methylated. Although CpG-rich and -poor promoters showed distinct methylation patterns, interestingly, a negative correlation between promoter methylation levels and gene transcription levels was consistently observed across promoters with high to low CpG densities. Importantly, we observed substantial interindividual variation in DNA methylation across the individual PBM methylomes and the pattern of this interindividual variation varied between different genomic features, with highly variable regions enriched for repetitive DNA elements. Furthermore, we observed a modest but significant excess (p < 2.2 × 10(-16)) of genes showing a negative correlation between interindividual promoter methylation and transcription levels. These significant genes were enriched in biological processes that are closely related to PBM functions, suggesting that alteration in DNA methylation is likely to be an important mechanism contributing to the interindividual variation in PBM function, and PBM-related phenotypic and disease-susceptibility variation in humans.This study represents a comprehensive analysis of the human PBM methylome and its interindividual variation. Our data provide a valuable resource for future epigenomic and multiomic studies, exploring biological and disease-related regulatory mechanisms in PBMs.

Dataset Information

The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.

Publications

The effect of genotype and in utero environment on interindividual variation in neonate DNA methylomes.

Similar Datasets

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