Evidence map›Paper›PMID 41265020›Full record

ArticlePsychoneuroendocrinology2026

Not all saliva samples are equal: The role of cellular heterogeneity in DNA methylation and epigenetic age analyses with biological and psychosocial factors.

Meingold H Chan, Mandy Meijer, Sarah M Merrill, Maggie P Y Fu, David Lin, Julia L MacIsaac, Jenna L Riis, Douglas A Granger, Elizabeth A Thomas, Michael S Kobor

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychoneuroendocrinology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Meingold H ChanEdwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada; Department of Human Development and Family Science, Purdue University, West Lafayette, IN, USA.
Mandy MeijerEdwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Sarah M MerrillDepartment of Psychology, University of Massachusetts Lowell, Lowell, MA, USA.
Maggie P Y FuEdwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
David LinBritish Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Julia L MacIsaacEdwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Jenna L RiisInstitute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, USA; Department of Health and Kinesiology, University of Illinois Urbana Champaign, Urbana, IL, USA.
Douglas A GrangerInstitute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, USA; Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Elizabeth A ThomasInstitute for Interdisciplinary Salivary Bioscience Research, University of California, Irvine, CA, USA; Department of Neurobiology and Behavior, University of California, Irvine, CA, USA.
Michael S KoborEdwin S. H. Leong Centre for Healthy Aging, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada; British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada; Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada. Electronic address: michael.kobor@ubc.ca.

Funding

Temperment, Psychobiological, and Cognitive PredictorsP01HD039667 · NICHD · UNIV OF NORTH CAROLINA CHAPEL HILL · PI BLAIR, CLANCY B · 2002 to 2011
$29.1M
Early Life Stress and the Environmental Origins of Disease: a Population-based Prospective Longitudinal Study of Children in Rural Poverty (ECHO)UH3OD023332 · OD · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI KOPP, LISA MICHELLE, SWINGLER, MARGARET M. · 2018 to 2022
$22.7M
Stress, Self-Regulation and Psychopathology in Middle ChildhoodR01HD081252 · NICHD · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI BLAIR, CLANCY B · 2015 to 2019
$6.5M
NICHD NIH HHS P01 HD039667NICHD NIH HHS R01 HD081252NIH HHS UH3 OD023332
6 · The paper itself

Abstract

Saliva is widely used in biomedical population research, including epigenetic analyses to investigate gene-environment interplay and identify biomarkers. Its minimally invasive collection procedure makes it ideal for studies in pediatric populations. Saliva is a heterogenous tissue composed of immune and buccal epithelial cells (BEC). Amongst the many epigenetic marks, DNA methylation (DNAm) is the most studied in human populations. DNAm profiles are often highly cell type (CT)-specific. CT composition can drive salivary DNAm associations with environments or health as well as epigenetic age acceleration (EAA), which is the discrepancy between chronological and biological age derived from DNAm. To address this, reference-based CT deconvolution and statistical adjustment with estimated CT in DNAm analyses have become a common practice. However, it remains unclear how different CT reference panels-constructed from adult versus pediatric samples-affect DNAm results. Additionally, whether DNAm and EAA associations in saliva primarily originate from immune cells or BECs, or if they persist across saliva samples despite varying CT proportions, still requires more investigations. The current study used salivary DNAm samples obtained from 529 children (mean age=7.26 years, SD=0.26 years) in a community-based cohort, the Family Life Project. Our results demonstrated that the child reference panel outperformed the adult one based on goodness of fit measure and highlighted the impact of estimated CT discrepancies across reference panels on DNAm associations. Upon stratifying the salivary DNAm samples into three subsamples-primarily BECs, primarily immune cells, and an approximately equal mix of both, we found significantly different EAAs across stratified samples when CT proportions were not accounted for. In both the contexts of DNAm and EAA associations, we detected stronger effects of cotinine concentrations, a tobacco smoke-exposure biomarker, in the subsample with primarily immune cells. We discussed the implications of our findings for the interpretation and replication of epigenetic research involving pediatric saliva samples.

Indexed as

AgingDNA MethylationEpigenesis, GeneticSalivaAdultAge FactorsBiomarkersChildChild, PreschoolEpithelial CellsFemaleHumansMaleBiomarkersCell type heterogeneityDNA methylationEpigenome-wide association studyFamily Life ProjectPediatric salivaReference-based cell type deconvolution

Identifiers

PMID41265020
PMCPMC13328854

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.