Dataset Information

Global and gene-specific DNA methylation across multiple tissues in early infancy: implications for children's health research.

ABSTRACT: An increasing number of population studies are assessing epigenetic variation in relation to early-life outcomes in tissues accessible to epidemiologic researchers. Epigenetic mechanisms are highly tissue specific, however, and it is unclear whether the variation observed in one of the tissue types is representative of other sources or whether the variation in DNA methylation is distinct, reflecting potential functional differences across tissues. To assess relations between DNA methylation in various samples from newborns and children in early infancy, we measured promoter or gene-body DNA methylation in matched term placenta, cord blood, and 3-6 mo saliva samples from 27 unrelated infants enrolled in the Rhode Island Child Health Study. We investigated 7 gene loci (KLF15, NR3C1, LEP, DEPTOR, DDIT4, HSD11B2, and CEBPB) and global methylation, using repetitive region LINE-1 and ALUYb8 sequences. We observed a great degree of interlocus, intertissue, and interindividual epigenetic variation in most of the analyzed loci. In correlation analyses, only cord blood NR3C1 promoter methylation correlated negatively with methylation in saliva. We conclude that placenta, cord blood, and saliva cannot be used as a substitute for one another to evaluate DNA methylation at these loci during infancy. Each tissue has a unique epigenetic signature that likely reflects their differential functions. Future studies should consider the uniqueness of these features, to improve epigenetic biomarker discovery and translation.

SUBMITTER: Armstrong DA

PROVIDER: S-EPMC3986842 | biostudies-other | 2014 May

REPOSITORIES: biostudies-other

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Global and gene-specific DNA methylation across multiple tissues in early infancy: implications for children's health research.

Armstrong David A DA Lesseur Corina C Conradt Elisabeth E Lester Barry M BM Marsit Carmen J CJ

FASEB journal : official publication of the Federation of American Societies for Experimental Biology 20140129 5

An increasing number of population studies are assessing epigenetic variation in relation to early-life outcomes in tissues accessible to epidemiologic researchers. Epigenetic mechanisms are highly tissue specific, however, and it is unclear whether the variation observed in one of the tissue types is representative of other sources or whether the variation in DNA methylation is distinct, reflecting potential functional differences across tissues. To assess relations between DNA methylation in v ...[more]

PMID: 24478308

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Project description:BackgroundDNA methylation is an important tissue-specific epigenetic event that influences transcriptional regulation of gene expression. Differentially methylated CpG sites may act as mediators between genetic variation and gene expression, and this relationship can be exploited while mapping multi-tissue expression quantitative trait loci (eQTL). Current multi-tissue eQTL mapping techniques are limited to only exploiting gene expression patterns across multiple tissues either in a joint tissue or tissue-by-tissue frameworks. We present a new statistical approach that enables us to model the effect of germ-line variation on tissue-specific gene expression in the presence of effects due to DNA methylation.ResultsOur method efficiently models genetic and epigenetic variation to identify genomic regions of interest containing combinations of mRNA transcripts, CpG sites, and SNPs by jointly testing for genotypic effect and higher order interaction effects between genotype, methylation and tissues. We demonstrate using Monte Carlo simulations that our approach, in the presence of both genetic and DNA methylation effects, gives an improved performance (in terms of statistical power) to detect eQTLs over the current eQTL mapping approaches. When applied to an array-based dataset from 150 neuropathologically normal adult human brains, our method identifies eQTLs that were undetected using standard tissue-by-tissue or joint tissue eQTL mapping techniques. As an example, our method identifies eQTLs by leveraging methylated CpG sites in a LIM homeobox member gene (LHX9), which may have a role in the neural development.ConclusionsOur score test-based approach does not need parameter estimation under the alternative hypothesis. As a result, our model parameters are estimated only once for each mRNA - CpG pair. Our model specifically studies the effects of non-coding regions of DNA (in this case, CpG sites) on mapping eQTLs. However, we can easily model micro-RNAs instead of CpG sites to study the effects of post-transcriptional events in mapping eQTL. Our model's flexible framework also allows us to investigate other genomic events such as alternative gene splicing by extending our model to include gene isoform-specific data.

Project description:Background"Decolonizing global health" (DGH) may help global health trainees understand and remediate the effects of historical colonialism on global health, but little is known regarding how trainees perceive DGH. Understanding their perspectives is critical for designing educational interventions tailored to their needs.ObjectivesTo understand how trainees perceive DGH research and to determine if perspectives differ between trainees from high- (HICs) versus low- and middle-income countries (LMICs).MethodsAn online survey of all 2017-2022 pre-doctoral and post-doctoral trainees (n = 111) and mentors (n = 91) within a multi-university program that supports US and international investigators in one-year mentored global health research. The survey evaluated individuals' self-reported knowledge and attitudes toward DGH and their perceptions of historical colonialism's impact on eight aspects of global health.FindingsThe response rate to trainee surveys was 56%. Trainees from LMICs were less aware of the concept of DGH; 5/25 (20%) had never heard of DGH and 16/25 (64%) reported that they "know a little," whereas all HIC trainees had heard of DGH and 29/36 (81%) reported that they "know a little" (p = 0.019). For three aspects of global health (i.e., which research questions get asked; development of collaborative relationships; and data/statistical analyses), trainees from LMICs were more likely to report positive effects of colonialism. However, in open-ended responses, no thematic differences existed between how LMIC and HIC trainees defined DGH (i.e., actively eliminating power imbalances; prioritizing local needs; promoting local leadership; providing equitable opportunities; and ensuring programs are culturally appropriate).ConclusionsDifferent perspectives surrounding what DGH means suggest a shared understanding may be needed and is arguably prerequisite to designing educational interventions to help global health trainees recognize, understand, and act in global health. Future research is needed to understand perspectives on decolonization across diverse contexts with attention to constructs such as race, ethnicity, and gender.

Dataset Information

Global and gene-specific DNA methylation across multiple tissues in early infancy: implications for children's health research.

Publications

Global and gene-specific DNA methylation across multiple tissues in early infancy: implications for children's health research.

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