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

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Title: Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study.
Authors: Yun Liu1 yun_liu@brown.edu, Eliot, Melissa N.1, Papandonatos, George D.2, Kelsey, Karl T.1,3, Fore, Ruby4, Langevin, Scott5, Buckley, Jessie6, Aimin Chen7, Lanphear, Bruce P.8, Cecil, Kim M.5,9,10, Yolton, Kimberly10, Hivert, Marie-France4,11, Sagiv, Sharon K.12, Baccarelli, Andrea A.13, Oken, Emily4, Braun, Joseph M.1
Source: Environmental Health Perspectives. Mar2022, Vol. 130 Issue 3, p037005-1-037005-12. 12p. 6 Charts, 1 Graph.
Subject Terms: *Biomarkers, *Fluorocarbons, *Molecular biology, Maternal exposure, Childbirth, Substance abuse, Leukocytes, Cognition, Cardiovascular diseases, Regression analysis, DNA methylation, Prenatal exposure delayed effects, Cord blood, Descriptive statistics, Genes, Tumors, Data analysis software, Epigenomics, Longitudinal method, Sulfur acids, Evaluation, Pregnancy
Geographic Terms: Ohio
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 (푛= 266) and peripheral leukocytes at 12 years of age (푛= 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, 푞< 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. [ABSTRACT FROM AUTHOR]
Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study.
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  Data: &lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Yun+Liu%22&quot;&gt;Yun Liu&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;i&gt; yun_liu@brown.edu&lt;/i&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Eliot%2C+Melissa+N%2E%22&quot;&gt;Eliot, Melissa N.&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Papandonatos%2C+George+D%2E%22&quot;&gt;Papandonatos, George D.&lt;/searchLink&gt;&lt;relatesTo&gt;2&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Kelsey%2C+Karl+T%2E%22&quot;&gt;Kelsey, Karl T.&lt;/searchLink&gt;&lt;relatesTo&gt;1,3&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Fore%2C+Ruby%22&quot;&gt;Fore, Ruby&lt;/searchLink&gt;&lt;relatesTo&gt;4&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Langevin%2C+Scott%22&quot;&gt;Langevin, Scott&lt;/searchLink&gt;&lt;relatesTo&gt;5&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Buckley%2C+Jessie%22&quot;&gt;Buckley, Jessie&lt;/searchLink&gt;&lt;relatesTo&gt;6&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Aimin+Chen%22&quot;&gt;Aimin Chen&lt;/searchLink&gt;&lt;relatesTo&gt;7&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Lanphear%2C+Bruce+P%2E%22&quot;&gt;Lanphear, Bruce P.&lt;/searchLink&gt;&lt;relatesTo&gt;8&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Cecil%2C+Kim+M%2E%22&quot;&gt;Cecil, Kim M.&lt;/searchLink&gt;&lt;relatesTo&gt;5,9,10&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Yolton%2C+Kimberly%22&quot;&gt;Yolton, Kimberly&lt;/searchLink&gt;&lt;relatesTo&gt;10&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Hivert%2C+Marie-France%22&quot;&gt;Hivert, Marie-France&lt;/searchLink&gt;&lt;relatesTo&gt;4,11&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Sagiv%2C+Sharon+K%2E%22&quot;&gt;Sagiv, Sharon K.&lt;/searchLink&gt;&lt;relatesTo&gt;12&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Baccarelli%2C+Andrea+A%2E%22&quot;&gt;Baccarelli, Andrea A.&lt;/searchLink&gt;&lt;relatesTo&gt;13&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Oken%2C+Emily%22&quot;&gt;Oken, Emily&lt;/searchLink&gt;&lt;relatesTo&gt;4&lt;/relatesTo&gt;&lt;br /&gt;&lt;searchLink fieldCode=&quot;AR&quot; term=&quot;%22Braun%2C+Joseph+M%2E%22&quot;&gt;Braun, Joseph M.&lt;/searchLink&gt;&lt;relatesTo&gt;1&lt;/relatesTo&gt;
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  Data: &lt;searchLink fieldCode=&quot;JN&quot; term=&quot;%22Environmental+Health+Perspectives%22&quot;&gt;Environmental Health Perspectives&lt;/searchLink&gt;. Mar2022, Vol. 130 Issue 3, p037005-1-037005-12. 12p. 6 Charts, 1 Graph.
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  Data: 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&#226;€“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 (푛= 266) and peripheral leukocytes at 12 years of age (푛= 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&#226;€™s age and gestational PFAS. We performed Gene Ontology enrichment analysis to identify molecular pathways. We used Project Viva (1999&#226;€“2002; Boston, Massachusetts) to replicate significant associations. RESULTS: After adjusting for covariates, 435 cytosine&#226;€“guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate, 푞&lt; 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&#226;€™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. [ABSTRACT FROM AUTHOR]
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  Data: &lt;i&gt;Copyright of Environmental Health Perspectives is the property of National Institute of Environmental Health Sciences and its content may not be copied or emailed to multiple sites without the copyright holder&#39;s express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.&lt;/i&gt; (Copyright applies to all Abstracts.)
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        Value: 10.1289/ehp10118
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        Text: English
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    Subjects:
      – SubjectFull: Biomarkers
        Type: general
      – SubjectFull: Fluorocarbons
        Type: general
      – SubjectFull: Molecular biology
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      – SubjectFull: Maternal exposure
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      – SubjectFull: DNA methylation
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      – SubjectFull: Genes
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      – SubjectFull: Sulfur acids
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      – SubjectFull: Pregnancy
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      – SubjectFull: Ohio
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              Text: Mar2022
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