PMID- 34798907 OWN - NLM STAT- MEDLINE DCOM- 20220131 LR - 20220131 IS - 1868-7083 (Electronic) IS - 1868-7075 (Print) IS - 1868-7075 (Linking) VI - 13 IP - 1 DP - 2021 Nov 19 TI - Prenatal metal exposure, cord blood DNA methylation and persistence in childhood: an epigenome-wide association study of 12 metals. PG - 208 LID - 10.1186/s13148-021-01198-z [doi] LID - 208 AB - BACKGROUND: Prenatal exposure to essential and non-essential metals impacts birth and child health, including fetal growth and neurodevelopment. DNA methylation (DNAm) may be involved in pathways linking prenatal metal exposure and health. In the Project Viva cohort, we analyzed the extent to which metals (As, Ba, Cd, Cr, Cs, Cu, Hg, Mg, Mn, Pb, Se, and Zn) measured in maternal erythrocytes were associated with differentially methylated positions (DMPs) and regions (DMRs) in cord blood and tested if associations persisted in blood collected in mid-childhood. We measured metal concentrations in first-trimester maternal erythrocytes, and DNAm in cord blood (N = 361) and mid-childhood blood (N = 333, 6-10 years) with the Illumina HumanMethylation450 BeadChip. For each metal individually, we tested for DMPs using linear models (considered significant at FDR < 0.05), and for DMRs using comb-p (Sidak p < 0.05). Covariates included biologically relevant variables and estimated cell-type composition. We also performed sex-stratified analyses. RESULTS: Pb was associated with decreased methylation of cg20608990 (CASP8) (FDR = 0.04), and Mn was associated with increased methylation of cg02042823 (A2BP1) in cord blood (FDR = 9.73 x 10(-6)). Both associations remained significant but attenuated in blood DNAm collected at mid-childhood (p < 0.01). Two and nine Mn-associated DMPs were identified in male and female infants, respectively (FDR < 0.05), with two and six persisting in mid-childhood (p < 0.05). All metals except Ba and Pb were associated with >/= 1 DMR among all infants (Sidak p < 0.05). Overlapping DMRs annotated to genes in the human leukocyte antigen (HLA) region were identified for Cr, Cs, Cu, Hg, Mg, and Mn. CONCLUSIONS: Prenatal metal exposure is associated with DNAm, including DMRs annotated to genes involved in neurodevelopment. Future research is needed to determine if DNAm partially explains the relationship between prenatal metal exposures and health outcomes. CI - (c) 2021. The Author(s). FAU - Bozack, Anne K AU - Bozack AK AUID- ORCID: 0000-0003-0046-5767 AD - Division of Environmental Health Sciences, School of Public Health, University of California Berkeley, 2121 Berkeley Way, Room 5302, Berkeley, CA, 94720, USA. FAU - Rifas-Shiman, Sheryl L AU - Rifas-Shiman SL AD - Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. FAU - Coull, Brent A AU - Coull BA AD - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. FAU - Baccarelli, Andrea A AU - Baccarelli AA AD - Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York City, NY, USA. FAU - Wright, Robert O AU - Wright RO AD - Department of Environmental Medicine and Public Health and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, NY, New York City, USA. FAU - Amarasiriwardena, Chitra AU - Amarasiriwardena C AD - Department of Environmental Medicine and Public Health and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, NY, New York City, USA. FAU - Gold, Diane R AU - Gold DR AD - Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. AD - Department of Environmental Health, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. AD - Harvard Medical School, Boston, MA, USA. FAU - Oken, Emily AU - Oken E AD - Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. FAU - Hivert, Marie-France AU - Hivert MF AD - Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. AD - Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. FAU - Cardenas, Andres AU - Cardenas A AD - Division of Environmental Health Sciences, School of Public Health, University of California Berkeley, 2121 Berkeley Way, Room 5302, Berkeley, CA, 94720, USA. andres.cardenas@berkeley.edu. AD - Center for Computational Biology, University of California, Berkeley, CA, USA. andres.cardenas@berkeley.edu. LA - eng GR - U2C ES026561/ES/NIEHS NIH HHS/United States GR - R01 HD034568/HD/NICHD NIH HHS/United States GR - R01 ES031259/ES/NIEHS NIH HHS/United States GR - UH3 OD023286/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20211119 PL - Germany TA - Clin Epigenetics JT - Clinical epigenetics JID - 101516977 SB - IM MH - Adult MH - DNA Methylation/*genetics/immunology MH - Epigenome/genetics/immunology MH - Female MH - Fetal Blood/*chemistry/immunology MH - Humans MH - Infant MH - Infant, Newborn MH - Pregnancy MH - Prenatal Diagnosis/methods/statistics & numerical data MH - Prenatal Exposure Delayed Effects/genetics PMC - PMC8605513 OTO - NOTNLM OT - DNA methylation OT - EWAS OT - Manganese OT - Metals OT - Prenatal exposure COIS- The authors declare they have no competing interests. EDAT- 2021/11/21 06:00 MHDA- 2022/02/01 06:00 PMCR- 2021/11/19 CRDT- 2021/11/20 05:24 PHST- 2021/09/17 00:00 [received] PHST- 2021/11/08 00:00 [accepted] PHST- 2021/11/20 05:24 [entrez] PHST- 2021/11/21 06:00 [pubmed] PHST- 2022/02/01 06:00 [medline] PHST- 2021/11/19 00:00 [pmc-release] AID - 10.1186/s13148-021-01198-z [pii] AID - 1198 [pii] AID - 10.1186/s13148-021-01198-z [doi] PST - epublish SO - Clin Epigenetics. 2021 Nov 19;13(1):208. doi: 10.1186/s13148-021-01198-z.