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Maternal blood metal concentrations and whole blood DNA methylation during pregnancy in the Early Autism Risk Longitudinal Investigation (EARLI)
- Source :
- Epigenetics, vol 17, iss 3, Epigenetics
- Publication Year :
- 2021
- Publisher :
- Taylor & Francis, 2021.
-
Abstract
- BackgroundMetals exposures have important health effects in pregnancy. The maternal epigenome may be responsive to these exposures. We tested whether metals are associated with concurrent differential maternal whole blood DNA methylation.MethodsIn the Early Autism Risk Longitudinal Investigation (EARLI) cohort, we measured first or second trimester maternal blood metals concentrations (cadmium, lead, mercury, manganese, and selenium) in 215 participants using inductively coupled plasma mass spectrometry. DNA methylation in maternal whole blood was measured in the same specimens on the Illumina 450K array (201 participants). 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 to elucidate downstream pathways.ResultsIn multiple linear regression, we observed hypermethylation at 11 DNA methylation sites associated with lead (FDR q-value CYP24A1, ASCL2, FAT1, SNX31, NKX6-2, LRC4C, BMP7, HOXC11, PCDH7, ZSCAN18, and VIPR2. Lead associated sites were enriched (FDR q-value ARID2. Manganese associated sites were enriched for cellular metabolism pathways (FDR q-value0.86).DiscussionSingle DNA methylation sites associated with lead and manganese may be potential biomarkers of exposure or implicate downstream gene pathways. Future studies should replicate our findings to characterize potential toxicological mechanisms of trace metals through the maternal epigenome.
- Subjects :
- 0301 basic medicine
Cancer Research
trace metals
Physiology
Reproductive health and childbirth
Maternal blood
Biology
Medical Biochemistry and Metabolomics
03 medical and health sciences
Epigenome
0302 clinical medicine
Pregnancy
medicine
Basic Helix-Loop-Helix Transcription Factors
Genetics
Humans
Homeobox
2.2 Factors relating to the physical environment
Autistic Disorder
Aetiology
Molecular Biology
Gene
Whole blood
Homeodomain Proteins
DNA methylation
Prevention
Confounding
Genes, Homeobox
DNA Methylation
medicine.disease
Maternal epigenome
030104 developmental biology
Genes
Metals
030220 oncology & carcinogenesis
Cohort
Autism
Female
Biochemistry and Cell Biology
Research Paper
Developmental Biology
Subjects
Details
- Database :
- OpenAIRE
- Journal :
- Epigenetics, vol 17, iss 3, Epigenetics
- Accession number :
- edsair.doi.dedup.....4552b73cbd728d39ebd5ffc4b1d3a6bd
- Full Text :
- https://doi.org/10.6084/m9.figshare.14363488