DNA extracted from saliva for methylation studies of psychiatric traits: evidence tissue specificity and relatedness to brain
Open accessAbstract
DNA methylation has become increasingly recognized in the etiology of psychiatric disorders. Because brain tissue is not accessible in living humans, epigenetic studies are most often conducted in blood. Saliva is often collected for genotyping studies but is rarely used to examine DNA methylation because the proportion of epithelial cells and leukocytes varies extensively between individuals. The goal of this study was to evaluate whether saliva DNA is informative for studies of psychiatric disorders. DNA methylation (HumanMethylation450 BeadChip) was assessed in saliva and blood samples from 64 adult African Americans. Analyses were conducted using linear regression adjusted for appropriate covariates, including estimated cellular proportions. DNA methylation from brain tissues (cerebellum, frontal cortex, entorhinal cortex, and superior temporal gyrus) was obtained from a publically available dataset. Saliva and blood methylation was clearly distinguishable though there was positive correlation overall. There was little correlation in CpG sites within relevant candidate genes. Correlated CpG sites were more likely to occur in areas of low CpG density (i.e., CpG shores and open seas). There was more variability in CpG sites from saliva than blood, which may reflect its heterogeneity. Finally, DNA methylation in saliva appeared more similar to patterns from each of the brain regions examined overall than methylation in blood. Thus, this study provides a framework for using DNA methylation from saliva and suggests that DNA methylation of saliva may offer distinct opportunities for epidemiological and longitudinal studies of psychiatric traits.
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DNA methylation patterns in saliva may be closer to that of brain tissue than DNA methylation in blood or buccal cells.
“it has been suggested that DNA methylation patterns in saliva may be closer to that of brain tissue than DNA methylation in blood or buccal cells (Braun et al., 2019;Lowe et al., 2013;Smith et al., 2015).”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Smith et al., 2015
The Results and Discussion report that saliva methylation appeared more similar to the brain regions examined than blood methylation did. The paper does not establish the same comparison with buccal cells; its Discussion cautions that epithelial cells from saliva should not be considered equivalent to buccal swabs without empirical evidence. No page numbers were provided in our copy. (LLM, conf=0.90)
Experimental — accuracy not yet measuredOverlap in DNA methylation levels measured in saliva, buccal cells and blood is limited.
“overlap in DNA methylation levels measured in saliva, buccal cells and blood is limited”
From The applied implications of epigenetics in anxiety, affective and stress-related disorders - A review and synthesis on psychosocial stress, psychotherapy and prevention (2020) · cites this paper as Smith et al., 2015
The Results (‘Correlation Between Saliva and Blood’; page unavailable) show tissue differences: blood and saliva samples clustered separately, and saliva significantly predicted blood methylation at 27.3% of CpG sites. But methylation was positively correlated at 88.5% of sites, and the Discussion says buccal swabs were unavailable. The paper therefore does not establish limited overlap across all three sample types. (LLM, conf=0.85)
Experimental — accuracy not yet measured
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- Authors
- Smith, A. K., Kilaru, V., Klengel, T., Mercer, K. B., Bradley, B., Conneely, K. N., Ressler, K. J., & Binder, E. B.
- Affiliations
- Emory University (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Smith, Alicia K.
- ORCID
- Venue
- American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
- Publisher
- Wiley
- Published
- 2014-10-29
- Volume
- 168
- Issue
- 1
- Pages
- 36-44
- ISSN
- 1552-4841 (ISSN-L)
- 1552-485X
- PMC
- PMC4610814
- OpenAlex
- W2010390756
- Cited by
- 355
- References
- 65
- Citations by year
- 2026: 20 · 2025: 27 · 2024: 17 · 2023: 22 · 2022: 37 · 2021: 36 · 2020: 33 · 2019: 39 · 2018: 43 · 2017: 40 · 2016: 24 · 2015: 15 · 2014: 1 · 2012: 1
- FWCI
- 10.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Medical Genetics Part B Neuropsychiatric Genetics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- National Institutes of Health (MH085806, MH071537, MH096764, HD071982)
- Brain and Behavior Research Foundation (19233)
- Howard Hughes Medical Institute
- European Research Council (281338)
- Behrens-Weise Foundation
- Max Planck Society
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- saliva DNA, DNA methylation, mental illness, blood DNA, tissue specificity, brain regions, CpG sites, African Americans, epigenetics
- MeSH terms
- Adult, Mental Disorders, Black or African American, Brain, DNA, Female, Humans, Male, Saliva, CpG Islands, DNA Methylation
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