Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies

Lowe, Robert; Gemma, Carolina; Beyan, Huriya; Hawa, M.; Bazeos, Alexandra; Leslie, Richard; Montpetit, Alexandre; Rakyan, Vardhman K.; Ramagopalan, Sreeram

doi:10.4161/epi.24362

Cited by 144 publications

(118 citation statements)

References 40 publications

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“…Furthermore, the use of a child sample in this study necessitated the use of minimally invasive DNA sampling techniques, namely buccal swabs and saliva. However, while tissue‐specific differences in DNA methylation have been documented,43 it has been suggested that buccal swabs may be more representative than other peripheral tissues such as blood in epigenetic studies 44. This is due to a reduced cell heterogeneity in buccal swabs, and because they originate from the same developmental pathways as brain tissue 44.…”

Section: Discussionmentioning

confidence: 99%

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

et al. 2015

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BackgroundHypothalamic–pituitary–adrenal (HPA) axis functioning has been implicated in the development of stress‐related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive behavior therapy (CBT).MethodsChildren with anxiety disorders were recruited into the Genes for Treatment project (GxT, N = 1,152). Polymorphisms of FKBP5 and GR were analyzed for association with response to CBT. Percentage DNA methylation at the FKBP5 and GR promoter regions was measured before and after CBT in a subset (n = 98). Linear mixed effect models were used to investigate the relationship between genotype, DNA methylation, and change in primary anxiety disorder severity (treatment response).ResultsTreatment response was not associated with FKBP5 and GR polymorphisms, or pretreatment percentage DNA methylation. However, change in FKBP5 DNA methylation was nominally significantly associated with treatment response. Participants who demonstrated the greatest reduction in severity decreased in percentage DNA methylation during treatment, whereas those with little/no reduction in severity increased in percentage DNA methylation. This effect was driven by those with one or more FKBP5 risk alleles, with no association seen in those with no FKBP5 risk alleles. No significant association was found between GR methylation and response.ConclusionsAllele‐specific change in FKBP5 methylation was associated with treatment response. This is the largest study to date investigating the role of HPA axis related genes in response to a psychological therapy. Furthermore, this is the first study to demonstrate that DNA methylation changes may be associated with response to psychological therapies in a genotype‐dependent manner.

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Section: Discussionmentioning

confidence: 99%

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

et al. 2015

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“…Analogous to gene expression, DNA methylation patterns are partially tissue specific; thus, appropriate sampling for the disease or exposure of interest is paramount. In this study, we examine site-specific changes in DNA methylation throughout the genome relative to current cigarette smoking and smoking-related phenotypes in buccal mucosa, a tissue that, in addition to being a major site of direct exposure, may have utility as a surrogate tissue in the study of smoking-related lung diseases, such as COPD (4,27).…”

Section: Discussionmentioning

confidence: 99%

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study

Wan

Qiu

Carey

et al. 2015

Am J Respir Cell Mol Biol

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DNA methylation is a complex, tissue-specific phenomenon that can reflect both endogenous factors and exogenous exposures. Buccal brushings represent an easily accessible source of DNA, which may be an appropriate surrogate tissue in the study of environmental exposures and chronic respiratory diseases. Buccal brushings were obtained from a subset of current and former smokers from the COPDGene study. Genome-wide DNA methylation data were obtained in the discovery cohort (n = 82) using the Illumina HumanMethylation450K array. Empirical Bayes methods were used to test for differential methylation by current smoking status at 468,219 autosomal CpG sites using linear models adjusted for age, sex, and race. Pyrosequencing was performed in a nonoverlapping replication cohort (n = 130). Current smokers were significantly younger than former smokers in both the discovery and replication cohorts. Seven CpG sites were associated with current smoking at a false discovery rate less than 0.05 in the discovery cohort. Six of the seven significant sites were pyrosequenced in the replication cohort; five CpG sites, including sites annotated to CYP1B1 and PARVA, were replicated. Correlations between cumulative smoke exposure and time since smoking cessation were observed in a subset of the significantly associated CpG sites. A significant correlation between reduced lung function and increased radiographic emphysema with methylation at cg02162897 (CYP1B1) was observed among female subjects. Site-specific methylation of DNA isolated from buccal mucosa is associated with exposure to cigarette smoke, and may provide insights into the mechanisms underlying differential susceptibility toward the development of smoking-related chronic respiratory diseases.

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“…Although these tissues may serve as valuable biomarkers of disease onset and/or progression, the question of which tissue is most likely to reflect the organ of interest-the brain-remains somewhat unresolved. Recent work comparing the utility of buccal versus blood cells as surrogate tissue for epigenomewide association studies (EWASs) found initial compelling evidence that buccal cells may be more informative than blood [76]. Specifically, buccal cells were found to be significantly hypomethylated compared with blood; this is an important distinction, as DNaseI hypersensitive sites are a strong predictor of regulatory activity and are often observed at low methylated regions.…”

Section: Tissue and Cell Specificity Of Epigenetic Marksmentioning

confidence: 97%

Epigenetic Epidemiology of Psychiatric Disorders

Uddin

Bustamante

Toyokawa

2014

Epigenetics in Psychiatry

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Buccals are likely to be a more informative surrogate tissue than blood for epigenome-wide association studies

Cited by 144 publications

References 40 publications

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

Hpa Axis Related Genes and Response to Psychological Therapies: Genetics and Epigenetics

Smoking-Associated Site-Specific Differential Methylation in Buccal Mucosa in the COPDGene Study

Epigenetic Epidemiology of Psychiatric Disorders

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