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

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. OBJECTIVE...

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Autores principales: Liu, Yun, Eliot, Melissa N., Papandonatos, George D., Kelsey, Karl T., Fore, Ruby, Langevin, Scott, Buckley, Jessie, Chen, Aimin, Lanphear, Bruce P., Cecil, Kim M., Yolton, Kimberly, Hivert, Marie-France, Sagiv, Sharon K., Baccarelli, Andrea A., Oken, Emily, Braun, Joseph M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Environmental Health Perspectives 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911098/
https://www.ncbi.nlm.nih.gov/pubmed/35266797
http://dx.doi.org/10.1289/EHP10118
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author Liu, Yun
Eliot, Melissa N.
Papandonatos, George D.
Kelsey, Karl T.
Fore, Ruby
Langevin, Scott
Buckley, Jessie
Chen, Aimin
Lanphear, Bruce P.
Cecil, Kim M.
Yolton, Kimberly
Hivert, Marie-France
Sagiv, Sharon K.
Baccarelli, Andrea A.
Oken, Emily
Braun, Joseph M.
author_facet Liu, Yun
Eliot, Melissa N.
Papandonatos, George D.
Kelsey, Karl T.
Fore, Ruby
Langevin, Scott
Buckley, Jessie
Chen, Aimin
Lanphear, Bruce P.
Cecil, Kim M.
Yolton, Kimberly
Hivert, Marie-France
Sagiv, Sharon K.
Baccarelli, Andrea A.
Oken, Emily
Braun, Joseph M.
author_sort Liu, Yun
collection PubMed
description 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 ([Formula: see text]) and peripheral leukocytes at 12 years of age ([Formula: see text]) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between [Formula: see text] 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, [Formula: see text]). 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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spelling pubmed-89110982022-03-11 Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study Liu, Yun Eliot, Melissa N. Papandonatos, George D. Kelsey, Karl T. Fore, Ruby Langevin, Scott Buckley, Jessie Chen, Aimin Lanphear, Bruce P. Cecil, Kim M. Yolton, Kimberly Hivert, Marie-France Sagiv, Sharon K. Baccarelli, Andrea A. Oken, Emily Braun, Joseph M. Environ Health Perspect Research 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 ([Formula: see text]) and peripheral leukocytes at 12 years of age ([Formula: see text]) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between [Formula: see text] 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, [Formula: see text]). 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 Environmental Health Perspectives 2022-03-10 /pmc/articles/PMC8911098/ /pubmed/35266797 http://dx.doi.org/10.1289/EHP10118 Text en https://ehp.niehs.nih.gov/about-ehp/licenseEHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted.
spellingShingle Research
Liu, Yun
Eliot, Melissa N.
Papandonatos, George D.
Kelsey, Karl T.
Fore, Ruby
Langevin, Scott
Buckley, Jessie
Chen, Aimin
Lanphear, Bruce P.
Cecil, Kim M.
Yolton, Kimberly
Hivert, Marie-France
Sagiv, Sharon K.
Baccarelli, Andrea A.
Oken, Emily
Braun, Joseph M.
Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
title Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
title_full Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
title_fullStr Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
title_full_unstemmed Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
title_short Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
title_sort gestational perfluoroalkyl substance exposure and dna methylation at birth and 12 years of age: a longitudinal epigenome-wide association study
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911098/
https://www.ncbi.nlm.nih.gov/pubmed/35266797
http://dx.doi.org/10.1289/EHP10118
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