{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Aung MT"],"funding":["National Institute of Environmental Health Sciences","NIA NIH HHS","NIEHS NIH HHS","NIMHD NIH HHS","National Institutes of Health","National Institute on Aging"],"pagination":["253-268"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8920182"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["17(3)"],"pubmed_abstract":["The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array. A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate <i>q</i>-value <0.1), near the genes <i>CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18</i>, and <i>VIPR2</i>. Lead-associated sites were enriched (FDR <i>q</i>-value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR <i>q</i>-value <0.1), one of which was near the gene <i>ARID2</i>. Manganese-associated sites were enriched for cellular metabolism pathways (FDR <i>q</i>-value<0.1). Effect estimates for DNA methylation sites associated (<i>p</i> < 0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ > 0.86). DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways."],"journal":["Epigenetics"],"pubmed_title":["Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI)."],"pmcid":["PMC8920182"],"funding_grant_id":["P30ES017885","R01 AG055406","R01 ES025531","R01 ES025574","R01ES017646","R01 ES017646","R01AG055406","P30 ES017885","R01ES016443","R01 ES016443","R01 AG067592","R01ES025574","R01ES025531","R01 MD013299"],"pubmed_authors":["Loch-Caruso R","Volk HE","Hertz-Picciotto I","Aung MT","Ladd-Acosta C","Feinberg JI","M Bakulski K","Mukherjee B","Croen LA","Newschaffer CJ","Fallin MD","F Dou J","D Meeker J"],"additional_accession":[]},"is_claimable":false,"name":"Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI).","description":"The maternal epigenome may be responsive to prenatal metals exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation. In the Early Autism Risk Longitudinal Investigation cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured on the Illumina 450 K array. A subset sample of 97 women had both measures available for analysis, all of whom did not report smoking during pregnancy. Linear regression was used to test for site-specific associations between individual metals and DNA methylation, adjusting for cell type composition and confounding variables. Discovery gene ontology analysis was conducted on the top 1,000 sites associated with each metal. We observed hypermethylation at 11 DNA methylation sites associated with lead (FDR False Discovery Rate <i>q</i>-value <0.1), near the genes <i>CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18</i>, and <i>VIPR2</i>. Lead-associated sites were enriched (FDR <i>q</i>-value <0.1) for the pathways cell adhesion, nervous system development, and calcium ion binding. Manganese was associated with hypermethylation at four DNA methylation sites (FDR <i>q</i>-value <0.1), one of which was near the gene <i>ARID2</i>. Manganese-associated sites were enriched for cellular metabolism pathways (FDR <i>q</i>-value<0.1). Effect estimates for DNA methylation sites associated (<i>p</i> < 0.05) with cadmium, lead, and manganese were highly correlated (Pearson ρ > 0.86). DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Mar","modification":"2026-05-09T19:51:27.903Z","creation":"2025-04-05T09:58:29.636Z"},"accession":"S-EPMC8920182","cross_references":{"pubmed":["33794742"],"doi":["10.1080/15592294.2021.1897059"]}}