Cited by 78Per- and polyfluoroalkyl substances researchEpigenetics and DNA MethylationBirth, Development, and Health

Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study

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Liu, Yun, Eliot, Melissa N., Papandonatos, George D., Kelsey, Karl T., Fore, Ruby, Langevin, Scott, Buckley, Jessie, Chen, Aimin +8 more·2022·Environmental Health Perspectives

Abstract

Background: DNA methylation alterations may underlie associations between gestational perfluoroalkyl substances (PFAS) exposure and later-life health outcomes. To the best of our knowledge, no longitudinal studies have examined the associations between gestational PFAS and DNA methylation. Objectives: We examined associations of gestational PFAS exposure with longitudinal DNA methylation measures at birth and in adolescence using the Health Outcomes and Measures of the Environment (HOME) Study (2003–2006; Cincinnati, Ohio). Methods: We quantified serum concentrations of perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), and perfluorohexane sulfonate (PFHxS) in mothers during pregnancy. We measured DNA methylation in cord blood (n=266) and peripheral leukocytes at 12 years of age (n=160) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between log2-transformed PFAS concentrations and repeated DNA methylation measures using linear regression with generalized estimating equations. We included interaction terms between children’s age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999–2002; Boston, Massachusetts) to replicate significant associations. Results: After adjusting for covariates, 435 cytosine–guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, q<0.05). Specifically, we identified 2 CpGs for PFOS, 12 for PFOA, 8 for PFHxS, and 413 for PFNA; none overlapped. Among these, 2 CpGs for PFOA and 4 for PFNA were replicated in Project Viva. Some of the PFAS-associated CpG sites annotated to gene regions related to cancers, cognitive health, cardiovascular disease, and kidney function. We found little evidence that the associations between PFAS and DNA methylation differed by children’s age. Discussion: In these longitudinal data, PFAS biomarkers were associated with differences in several CpGs at birth and at 12 years of age in or near genes linked to some PFAS-associated health outcomes. Future studies should examine whether DNA methylation mediates associations between gestational PFAS exposure and health. https://doi.org/10.1289/EHP10118

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  • Prenatal PFAS-associated DNA methylation changes identified in the Project Viva cohort-specifically, 435 CpG sites altered in cord blood and persisting into childhood-include loci associated with neural, metabolic, and cognitive health.

    “Prenatal PFAS-associated DNA methylation changes identified in the Project Viva cohort—specifically, 435 CpG sites altered in cord blood and persisting into childhood—include loci associated with neural, metabolic, and cognitive health [67].”

    From Exposure to Per- and Polyfluoroalkyl Substances (PFASs) in Healthcare: Environmental and Clinical Insights (2025) · cites this paper as [67]

    The Results (page not provided) identify 435 PFAS-associated CpG sites in the HOME Study, with associations generally consistent at birth and age 12; only six of those sites were replicated in Project Viva. The Discussion (page not provided) links some identified gene regions to neural development, obesity, and cognitive health. The claim incorrectly places the 435-site finding in Project Viva. (LLM, conf=0.92)

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Research works printed but not linked: 2

  1. ATSDR (Agency for Toxic Substances and Disease Registry). 2018. Toxicological Profile for Perfluoroalkyls. https://wwwn.cdc.gov/TSP/ToxProfiles/ToxProfiles.aspx?id=1117&tid=237 [accessed 13 December 2021]. 37220203
  2. Belaya K, Finlayson S, Slater CR, Cossins J, Liu WW, Maxwell S, et al. 2012. Mutations in DPAGT1 cause a limb-girdle congenital myasthenic syndrome with tubular aggregates. Am J Hum Genet 91(1): 193– 201, PMID:, 10.1016/j.ajhg.201ok2.05.022. 22742743 PMC3397259 · DOI

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Authors
Liu, Y., Eliot, M. N., Papandonatos, G. D., Kelsey, K. T., Fore, R., Langevin, S., Buckley, J., Chen, A., Lanphear, B. P., Cecil, K. M., Yolton, K., Hivert, M.-F., Sagiv, S. K., Baccarelli, A. A., Oken, E., & Braun, J. M.
Affiliations
  • Brown University (US)
  • Harvard University (US)
  • University of Cincinnati (US)
  • Johns Hopkins University (US)
  • University of Pennsylvania (US)
  • Simon Fraser University (CA)
  • Cincinnati Children's Hospital Medical Center (US)
  • University of California, Berkeley (US)
  • Columbia University (US)
Corresponding author
Liu, Yun
Venue
Environmental Health Perspectives
Published
2022-03
Volume
130
Issue
3
Pages
37005-37005
ISSN
  • 0091-6765 (ISSN-L)
  • 1552-9924
OpenAlex
W4220903784
Cited by
78
References
82
Citations by year
2026: 17 · 2025: 23 · 2024: 15 · 2023: 16 · 2022: 7
FWCI
5.40
Type
journal article
Language
en
Open access
Licence
public-domain
Locations
  • Environmental Health Perspectives (publishedVersion, public-domain)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, public-domain)
Funders
  • National Institutes of Health (UH3OD023286, UG3OD023286)
  • National Institute of Environmental Health Sciences (R01ES030078, R01ES020349, R01ES027224, L40 ES032257, P01ES011261, R01ES032836, R01ES025214)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD034568)
Topics
  • Physical Sciences › Environmental Science › Environmental Chemistry › Per- and polyfluoroalkyl substances research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
perfluorinated compounds, prenatal exposure, DNA methylation, epigenetics, perfluorooctanoic acid, PFOS, perfluorononanoate, PFHxS, umbilical cord blood, prenatal environmental exposure, cancer risk, cognitive health, cardiovascular disease, renal function, home study
MeSH terms
Epigenome, Adolescent, Child, Environmental Pollutants, Female, Fluorocarbons, Humans, Infant, Newborn, Longitudinal Studies, Pregnancy, Alkanesulfonic Acids, DNA Methylation

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