ArticleClinical epigenetics2026
Comparison of DNA methylation measured in saliva and peripheral blood as a marker of exposure and outcome: a scoping review.
Article in Clinical epigenetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundEpigenetics represents a key mechanism through which environmental factors can influence the risk of developing chronic diseases. DNA methylation is tissue-specific, but some tissues share similar methylation patterns. Most studies investigating DNA methylation as a biomarker of exposure or health outcomes focus on blood; however, saliva, accessible and non-invasive, could be a valid alternative for population-based and longitudinal studies.
methodsWe conducted a scoping review following a systematic approach and reported findings according to PRISMA guidelines. We compared DNA methylation patterns between blood and saliva, including their correlation, correlation with a third tissue, and associations with exposures or health outcomes. PubMed was searched using predefined terms, and additional studies were identified via snowballing. Eligible studies measured DNA methylation in both blood and saliva from the same individuals. We excluded studies comparing tissues solely to identify differentially methylated sites, studies not using genomic DNA, and non-human studies.
resultsFifteen studies involving adults and children were included: seven cross-sectional, six cohort, one case series, and one case-control. Eight studies conducted epigenome-wide analyses (EWAS), six focused on specific loci (two assessing global methylation via repetitive elements such as LINE1, Alu, and Sat2), and one analyzed global methylation only. Among four exposure-specific studies, one reported association in both blood and saliva, while three found exposure- and locus-specific differences. Of two outcome-specific studies, one observed association in saliva only, and the other in both tissues at different loci. Two studies compared methylation with brain tissue: saliva showed slightly higher average correlation, whereas blood had stronger correlations at specific CpG sites. Among twelve studies directly comparing blood and saliva, ten reported high correlations. Many studies report small differences in DNA methylation; despite potential measurement error, these differences can be reliably detected in adequately powered studies.
conclusionsSaliva is a promising alternative tissue for epigenetic research. Baseline DNA methylation profiles are highly correlated with blood, and small differences can be reliably identified. Given its non-invasive and accessible collection, saliva is suitable for longitudinal, pediatric, and large-scale studies, provided that new markers are interpreted with caution and validated in independent cohorts.
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