Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study
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. We examined associati...
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| Veröffentlicht in: | Environmental health perspectives 2022-03, Vol.130 (3), p.37005 |
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| creator | 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 |
| description | 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.
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).
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 (
) and peripheral leukocytes at 12 years of age (
) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between
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.
After adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate,
). 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.
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. |
| doi_str_mv | 10.1289/EHP10118 |
| format | Article |
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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).
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 (
) and peripheral leukocytes at 12 years of age (
) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between
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.
After adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate,
). 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.
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.</description><identifier>ISSN: 0091-6765</identifier><identifier>EISSN: 1552-9924</identifier><identifier>DOI: 10.1289/EHP10118</identifier><identifier>PMID: 35266797</identifier><language>eng</language><publisher>United States: National Institute of Environmental Health Sciences</publisher><subject>Adolescent ; Alkanesulfonic Acids ; Child ; Child development ; DNA Methylation ; Environmental aspects ; Environmental Pollutants ; Epigenetic inheritance ; Epigenome ; Female ; Fluorocarbons ; Genetic aspects ; Health aspects ; Humans ; Infant, Newborn ; Longitudinal Studies ; Pediatric research ; Pregnancy ; Prenatal influences</subject><ispartof>Environmental health perspectives, 2022-03, Vol.130 (3), p.37005</ispartof><rights>COPYRIGHT 2022 National Institute of Environmental Health Sciences</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c576t-e61767219001aa7201f380927638e0c915448be26eb01113a5b425857cb59f903</citedby><cites>FETCH-LOGICAL-c576t-e61767219001aa7201f380927638e0c915448be26eb01113a5b425857cb59f903</cites><orcidid>0000-0002-2302-1600 ; 0000-0001-7752-2585 ; 0000-0002-4458-0516 ; 0000-0001-7976-0157 ; 0000-0001-7031-1216 ; 0000-0002-2979-9552 ; 0000-0001-8233-5485</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911098/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911098/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35266797$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Liu, Yun</creatorcontrib><creatorcontrib>Eliot, Melissa N</creatorcontrib><creatorcontrib>Papandonatos, George D</creatorcontrib><creatorcontrib>Kelsey, Karl T</creatorcontrib><creatorcontrib>Fore, Ruby</creatorcontrib><creatorcontrib>Langevin, Scott</creatorcontrib><creatorcontrib>Buckley, Jessie</creatorcontrib><creatorcontrib>Chen, Aimin</creatorcontrib><creatorcontrib>Lanphear, Bruce P</creatorcontrib><creatorcontrib>Cecil, Kim M</creatorcontrib><creatorcontrib>Yolton, Kimberly</creatorcontrib><creatorcontrib>Hivert, Marie-France</creatorcontrib><creatorcontrib>Sagiv, Sharon K</creatorcontrib><creatorcontrib>Baccarelli, Andrea A</creatorcontrib><creatorcontrib>Oken, Emily</creatorcontrib><creatorcontrib>Braun, Joseph M</creatorcontrib><title>Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study</title><title>Environmental health perspectives</title><addtitle>Environ Health Perspect</addtitle><description>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.
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).
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 (
) and peripheral leukocytes at 12 years of age (
) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between
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.
After adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate,
). 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.
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.</description><subject>Adolescent</subject><subject>Alkanesulfonic Acids</subject><subject>Child</subject><subject>Child development</subject><subject>DNA Methylation</subject><subject>Environmental aspects</subject><subject>Environmental Pollutants</subject><subject>Epigenetic inheritance</subject><subject>Epigenome</subject><subject>Female</subject><subject>Fluorocarbons</subject><subject>Genetic aspects</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infant, Newborn</subject><subject>Longitudinal Studies</subject><subject>Pediatric research</subject><subject>Pregnancy</subject><subject>Prenatal influences</subject><issn>0091-6765</issn><issn>1552-9924</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkt-K1DAYxYso7uwq-AQSEGS96Jqk0zTxQqjruLswuovjH7wqafq1jabN0KSy8xS-spkdd9nCXEguAjm_c0JOvih6RvAJoVy8XpxfEUwIfxDNSJrSWAg6fxjNMBYkZhlLD6JD535ijAln7HF0kKSUsUxks-jPGTgvvba9NOgKhtqMdrDS_NoYtBrLoPUK0OJ6bd04AJJ9hd5_ytFH8O3G3PiQ9OidHnx7IxKKfoAcHLI1yht4g3K0tH2j_Vjp7RWLtW6gtx3E33UFKHfOKr3LWQVm8yR6VEvj4Om__Sj6-mHx5fQ8Xl6eXZzmy1ilGfMxMJKxjBIRniRlRjGpE44FzVjCAStB0vmcl0AZlKEXksi0nNOUp5kqU1ELnBxFb3e567HsoFLQ-0GaYj3oTg6bwkpdTJVet0VjfxdcEIIFDwEvdgGNNFDovrYBU512qsiZYJwyLLJAxXuo0ACETNtDrcPxhD_Zw4dVQafVXsOriSEwHq59I0fniovV5_9nL79N2Zf32Bak8a2zZtz-lJuCxztQDda5Aeq7DgkutsNZ3A5nQJ_f7_wOvJ3G5C9ogNuG</recordid><startdate>20220301</startdate><enddate>20220301</enddate><creator>Liu, Yun</creator><creator>Eliot, Melissa N</creator><creator>Papandonatos, George D</creator><creator>Kelsey, Karl T</creator><creator>Fore, Ruby</creator><creator>Langevin, Scott</creator><creator>Buckley, Jessie</creator><creator>Chen, Aimin</creator><creator>Lanphear, Bruce P</creator><creator>Cecil, Kim M</creator><creator>Yolton, Kimberly</creator><creator>Hivert, Marie-France</creator><creator>Sagiv, Sharon K</creator><creator>Baccarelli, Andrea A</creator><creator>Oken, Emily</creator><creator>Braun, Joseph M</creator><general>National Institute of Environmental Health Sciences</general><general>Environmental Health Perspectives</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2302-1600</orcidid><orcidid>https://orcid.org/0000-0001-7752-2585</orcidid><orcidid>https://orcid.org/0000-0002-4458-0516</orcidid><orcidid>https://orcid.org/0000-0001-7976-0157</orcidid><orcidid>https://orcid.org/0000-0001-7031-1216</orcidid><orcidid>https://orcid.org/0000-0002-2979-9552</orcidid><orcidid>https://orcid.org/0000-0001-8233-5485</orcidid></search><sort><creationdate>20220301</creationdate><title>Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study</title><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></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c576t-e61767219001aa7201f380927638e0c915448be26eb01113a5b425857cb59f903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Adolescent</topic><topic>Alkanesulfonic Acids</topic><topic>Child</topic><topic>Child development</topic><topic>DNA Methylation</topic><topic>Environmental aspects</topic><topic>Environmental Pollutants</topic><topic>Epigenetic inheritance</topic><topic>Epigenome</topic><topic>Female</topic><topic>Fluorocarbons</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>Humans</topic><topic>Infant, Newborn</topic><topic>Longitudinal Studies</topic><topic>Pediatric research</topic><topic>Pregnancy</topic><topic>Prenatal influences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Liu, Yun</creatorcontrib><creatorcontrib>Eliot, Melissa N</creatorcontrib><creatorcontrib>Papandonatos, George D</creatorcontrib><creatorcontrib>Kelsey, Karl T</creatorcontrib><creatorcontrib>Fore, Ruby</creatorcontrib><creatorcontrib>Langevin, Scott</creatorcontrib><creatorcontrib>Buckley, Jessie</creatorcontrib><creatorcontrib>Chen, Aimin</creatorcontrib><creatorcontrib>Lanphear, Bruce P</creatorcontrib><creatorcontrib>Cecil, Kim M</creatorcontrib><creatorcontrib>Yolton, Kimberly</creatorcontrib><creatorcontrib>Hivert, Marie-France</creatorcontrib><creatorcontrib>Sagiv, Sharon K</creatorcontrib><creatorcontrib>Baccarelli, Andrea A</creatorcontrib><creatorcontrib>Oken, Emily</creatorcontrib><creatorcontrib>Braun, Joseph M</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Opposing Viewpoints Resource Center</collection><collection>Gale In Context: Science</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Environmental health perspectives</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Liu, Yun</au><au>Eliot, Melissa N</au><au>Papandonatos, George D</au><au>Kelsey, Karl T</au><au>Fore, Ruby</au><au>Langevin, Scott</au><au>Buckley, Jessie</au><au>Chen, Aimin</au><au>Lanphear, Bruce P</au><au>Cecil, Kim M</au><au>Yolton, Kimberly</au><au>Hivert, Marie-France</au><au>Sagiv, Sharon K</au><au>Baccarelli, Andrea A</au><au>Oken, Emily</au><au>Braun, Joseph M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study</atitle><jtitle>Environmental health perspectives</jtitle><addtitle>Environ Health Perspect</addtitle><date>2022-03-01</date><risdate>2022</risdate><volume>130</volume><issue>3</issue><spage>37005</spage><pages>37005-</pages><issn>0091-6765</issn><eissn>1552-9924</eissn><abstract>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.
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).
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 (
) and peripheral leukocytes at 12 years of age (
) using the Illumina HumanMethylation EPIC BeadChip. We analyzed associations between
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.
After adjusting for covariates, 435 cytosine-guanine dinucleotide (CpG) sites were associated with PFAS (false discovery rate,
). 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.
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.</abstract><cop>United States</cop><pub>National Institute of Environmental Health Sciences</pub><pmid>35266797</pmid><doi>10.1289/EHP10118</doi><orcidid>https://orcid.org/0000-0002-2302-1600</orcidid><orcidid>https://orcid.org/0000-0001-7752-2585</orcidid><orcidid>https://orcid.org/0000-0002-4458-0516</orcidid><orcidid>https://orcid.org/0000-0001-7976-0157</orcidid><orcidid>https://orcid.org/0000-0001-7031-1216</orcidid><orcidid>https://orcid.org/0000-0002-2979-9552</orcidid><orcidid>https://orcid.org/0000-0001-8233-5485</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adolescent Alkanesulfonic Acids Child Child development DNA Methylation Environmental aspects Environmental Pollutants Epigenetic inheritance Epigenome Female Fluorocarbons Genetic aspects Health aspects Humans Infant, Newborn Longitudinal Studies Pediatric research Pregnancy Prenatal influences |
| title | Gestational Perfluoroalkyl Substance Exposure and DNA Methylation at Birth and 12 Years of Age: A Longitudinal Epigenome-Wide Association Study |
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