Genome-wide analysis of DNA methylation in buccal cells: a study of monozygotic twins and mQTLs

Dongen, Jenny van; Ehli, Erik A.; Jansen, Ritsert C.; Beijsterveldt, Catharina E. M. van; Willemsen, Gonneke; Hottenga, Jouke Jan; Kallsen, Noah A.; Peyton, Stephen; Breeze, Charles E.; Kluft, C.; Heijmans, Bastiaan T.; Bartels, Meike; Davies, Gareth E.; Boomsma, Dorret I.

doi:10.1186/s13072-018-0225-x

Cited by 46 publications

(47 citation statements)

References 39 publications

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“…22 The chip has been used and evaluated in a number of recent studies. 23,24 Epigenome-wide association studies (EWAS) assess methylation of the DNA and its associations with gene expression, phenotypes or exposures. Although epigenetics as a general term also include histone modifications and other mechanisms that may alter gene expression, EWAS have been most widely used to study DNA methylation.…”

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confidence: 99%

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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Objective Asthma is a common chronic respiratory airway disease influenced by environmental factors and possibly their interaction with the human genome causing epigenetic changes. Epigenome‐wide association studies (EWAS) have mainly investigated DNA methylation and its association with disease or traits, exposure factors or gene expression. This systematic review aimed to identify all EWAS assessing differentially methylated sites associated with asthma in humans. Design Structured systematic literature search following PRISMA guidelines, Newcastle‐Ottawa Scale (NOS) for cohort studies was used for bias assessment. Data Sources We searched PubMed and Embase databases from 2005 to 2019. Eligibility Criteria Epigenome‐wide association studies testing association between differential methylation and asthma in humans. Results Overall, we identified 16 EWAS studies complying with our search criteria. Twelve studies were conducted on children, and 10 were conducted on sample sizes <150 subjects. Four hundred and nineteen CpGs were reported in children studies after correction for multiple testing. In the adult studies, thousands of differentially methylated sites were identified. Differential methylation in inflammatory‐related genes correlated with higher levels of gene expressions of inflammatory modulators in asthma. Differentially methylated genes associated with asthma included SMAD3, SERPINC1, PROK1, IL13, RUNX3 and TIGIT. Forty‐one CpGs were replicated at least once in blood samples, and 28 CpGs were replicated in nasal samples. Conclusion Although many differentially methylated CpGs in genes known to be involved in asthma have been identified in EWAS to date, we conclude that further studies of larger sample sizes and analyses of differential methylation between different phenotypes are needed in order to comprehensively evaluate the role of epigenetic factors in the pathophysiology and heterogeneity of asthma, and the potential clinical utility to predict or classify patients with asthma.

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confidence: 99%

Epigenome‐wide association studies in asthma: A systematic review

Edris

Dekker

Melén

et al. 2019

Clin Experimental Allergy

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Section: Resultsmentioning

confidence: 93%

“…Finally, we compared our results for overlap with previously reported methylation quantitative trait loci (mQTLs) in buccal cells 31 , which contain a similar composition of epithelial cells as saliva 32 . We assessed the overlap of our significant sites that surpassed biological threshold with significant mQTLs within a distance of 1 Mb in a recent study of buccal cells in a sample of males and females (mean age 7.5 years) 31 . Out of 723 sex-related sites, 67 (9.27%) were associated with an mQTL in buccal cells, which is more than would be expected by chance (OR=2.3, overlapping p value=4.9e -09 ), and 45 out of 566 time-related sites were associated with mQTLs (7.96%; OR=1.9, overlapping p value=5.6e -05 ).…”

Section: Resultsmentioning

confidence: 93%

“…Summary statistics were obtained from the corresponding author of a prior publication 31 to test for overlap of sex-and time-related CpG sites with previously reported methylation quantitative trait loci (mQTLs). The GeneOverlap 55 package in R was used to obtain odds ratios and p values from the Fisher's exact test for overlap relative to quality controlled EPIC array probes (n = 794811).…”

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confidence: 99%

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Distinctions between sex and time in patterns of DNA methylation across puberty

Moore

Humphreys

Colich

et al. 2019

Preprint

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Background There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition.Methods In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. We targeted two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.Results Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition.Conclusions These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.

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“…We compared our results for overlap with previously reported methylation quantitative trait loci (mQTLs) in buccal cells 56 , which contain a similar composition of epithelial cells as saliva 57 . Summary statistics were obtained from the corresponding author of a prior publication 56 to test for overlap of sex-and timerelated CpG sites with previously reported methylation quantitative trait loci (mQTLs). The GeneOverlap 55 package in R was used to obtain odds ratios and p values from the Fisher's exact test for overlap relative to quality controlled EPIC array probes (794811).…”

Section: Enrichments For Genomic Context Mqtls and Androgen Responsmentioning

confidence: 92%

Distinctions between sex and time in patterns of DNA methylation across puberty

Moore

Humphreys

Colich

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: There are significant sex differences in human physiology and disease; the genomic sources of these differences, however, are not well understood. During puberty, a drastic neuroendocrine shift signals physical changes resulting in robust sex differences in human physiology. Here, we explore how shifting patterns of DNA methylation may inform these pathways of biological plasticity during the pubertal transition. In this study we analyzed DNA methylation (DNAm) in saliva at two time points across the pubertal transition within the same individuals. Our purpose was to compare two domains of DNAm patterns that may inform processes of sexual differentiation 1) sex related sites, which demonstrated differences between males from females and 2) time related sites in which DNAm shifted significantly between timepoints. We further explored the correlated network structure sex and time related DNAm networks and linked these patterns to pubertal stage, assays of salivary testosterone, a reliable diagnostic of free, unbound hormone that is available to act on target tissues, and overlap with androgen response elements.Results: Sites that differed by biological sex were largely independent of sites that underwent change across puberty. Time-related DNAm sites, but not sex-related sites, formed correlated networks that were associated with pubertal stage. Both time and sex DNAm networks reflected salivary testosterone levels that were enriched for androgen response elements, with sex-related DNAm networks being informative of testosterone levels above and beyond biological sex later in the pubertal transition. Conclusions: These results inform our understanding of the distinction between sex- and time-related differences in DNAm during the critical period of puberty and highlight a novel linkage between correlated patterns of sex-related DNAm and levels of salivary testosterone.

show abstract

Genome-wide analysis of DNA methylation in buccal cells: a study of monozygotic twins and mQTLs

Cited by 46 publications

References 39 publications

Epigenome‐wide association studies in asthma: A systematic review

Epigenome‐wide association studies in asthma: A systematic review

Distinctions between sex and time in patterns of DNA methylation across puberty

Distinctions between sex and time in patterns of DNA methylation across puberty

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