Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study
Background: Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to p...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-05-01
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| Series: | Environment International |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S016041202200109X |
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| author | Gillian England-Mason Sarah M. Merrill Nicole Gladish Sarah R. Moore Gerald F. Giesbrecht Nicole Letourneau Julia L. MacIsaac Amy M. MacDonald David W. Kinniburgh Anne-Louise Ponsonby Richard Saffery Jonathan W. Martin Michael S. Kobor Deborah Dewey |
| author_facet | Gillian England-Mason Sarah M. Merrill Nicole Gladish Sarah R. Moore Gerald F. Giesbrecht Nicole Letourneau Julia L. MacIsaac Amy M. MacDonald David W. Kinniburgh Anne-Louise Ponsonby Richard Saffery Jonathan W. Martin Michael S. Kobor Deborah Dewey |
| author_sort | Gillian England-Mason |
| collection | DOAJ |
| description | Background: Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood. Objective: Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs). Methods: Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders. Results: One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs. Discussion: Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed. |
| first_indexed | 2024-04-13T06:41:12Z |
| format | Article |
| id | doaj.art-82e2a50fcf3f4ec7b4a1c080bb1a5b22 |
| institution | Directory Open Access Journal |
| issn | 0160-4120 |
| language | English |
| last_indexed | 2024-04-13T06:41:12Z |
| publishDate | 2022-05-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Environment International |
| spelling | doaj.art-82e2a50fcf3f4ec7b4a1c080bb1a5b222022-12-22T02:57:43ZengElsevierEnvironment International0160-41202022-05-01163107183Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association studyGillian England-Mason0Sarah M. Merrill1Nicole Gladish2Sarah R. Moore3Gerald F. Giesbrecht4Nicole Letourneau5Julia L. MacIsaac6Amy M. MacDonald7David W. Kinniburgh8Anne-Louise Ponsonby9Richard Saffery10Jonathan W. Martin11Michael S. Kobor12Deborah Dewey13Department of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, CanadaDepartment of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, CanadaDepartment of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, CanadaDepartment of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, CanadaDepartment of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Psychology, Faculty of Arts, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, CanadaDepartment of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Faculty of Nursing, University of Calgary, Calgary, Alberta, Canada; Department of Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Calgary, Alberta, CanadaDepartment of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, CanadaAlberta Centre for Toxicology, University of Calgary, Calgary, Alberta, CanadaAlberta Centre for Toxicology, University of Calgary, Calgary, Alberta, Canada; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Alberta, CanadaMurdoch Children’s Research Institute, Royal Children’s Hospital, University of Melbourne, Melbourne, Victoria, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, University of Melbourne, Melbourne, Victoria, AustraliaScience for Life Laboratory, Department of Environmental Science, Stockholm University, Stockholm, Södermanland, SwedenDepartment of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children’s Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; Centre for Molecular Medicine and Therapeutics, Vancouver, British Columbia, Canada; Program in Child and Brain Development, CIFAR, Toronto, Ontario, CanadaDepartment of Paediatrics, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Owerko Centre, Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Alberta, Canada; Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; Hotchkiss Brain Institute, Calgary, Alberta, Canada; Corresponding author at: Department of Paediatrics, University of Calgary, #397 Owerko Center, Child Development Centre, 2500 University Dr. NW, Calgary, Alberta T2N 1N4, Canada.Background: Prenatal exposure to phthalates has been associated with adverse health and neurodevelopmental outcomes. DNA methylation (DNAm) alterations may be a mechanism underlying these effects, but prior investigations of prenatal exposure to phthalates and neonatal DNAm profiles are limited to placental tissue and umbilical cord blood. Objective: Conduct an epigenome-wide association study (EWAS) of the associations between prenatal exposure to phthalates and DNAm in two accessible infant tissues, venous buffy coat blood and buccal epithelial cells (BECs). Methods: Participants included 152 maternal-infant pairs from the Alberta Pregnancy Outcomes and Nutrition (APrON) study. Maternal second trimester urine samples were analyzed for nine phthalate metabolites. Blood (n = 74) or BECs (n = 78) were collected from 3-month-old infants and profiled for DNAm using the Infinium HumanMethylation450 (450K) BeadChip. Robust linear regressions were used to investigate the associations between high (HMWPs) and low molecular weight phthalates (LMWPs) and change in methylation levels at variable Cytosine-phosphate-Guanine (CpG) sites in infant tissues, as well as the sensitivity of associations to potential confounders. Results: One candidate CpG in gene RNF39 reported by a previous study examining prenatal exposure to phthalates and cord blood DNAm was replicated. The EWAS identified 12 high-confidence CpGs in blood and another 12 in BECs associated with HMWPs and/or LMWPs. Prenatal exposure to bisphenol A (BPA) associated with two of the CpGs associated with HMWPs in BECs. Discussion: Prenatal exposure to phthalates was associated with DNAm variation at CpGs annotated to genes associated with endocrine hormone activity (i.e., SLCO4A1, TPO), immune pathways and DNA damage (i.e., RASGEF1B, KAZN, HLA-A, MYO18A, DIP2C, C1or109), and neurodevelopment (i.e., AMPH, NOTCH3, DNAJC5). Future studies that characterize the stability of these associations in larger samples, multiple cohorts, across tissues, and investigate the potential associations between these biomarkers and relevant health and neurodevelopmental outcomes are needed.http://www.sciencedirect.com/science/article/pii/S016041202200109XPhthalatesNeurodevelopmentEpigenetics450KDNA methylationAPrON study |
| spellingShingle | Gillian England-Mason Sarah M. Merrill Nicole Gladish Sarah R. Moore Gerald F. Giesbrecht Nicole Letourneau Julia L. MacIsaac Amy M. MacDonald David W. Kinniburgh Anne-Louise Ponsonby Richard Saffery Jonathan W. Martin Michael S. Kobor Deborah Dewey Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study Environment International Phthalates Neurodevelopment Epigenetics 450K DNA methylation APrON study |
| title | Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study |
| title_full | Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study |
| title_fullStr | Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study |
| title_full_unstemmed | Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study |
| title_short | Prenatal exposure to phthalates and peripheral blood and buccal epithelial DNA methylation in infants: An epigenome-wide association study |
| title_sort | prenatal exposure to phthalates and peripheral blood and buccal epithelial dna methylation in infants an epigenome wide association study |
| topic | Phthalates Neurodevelopment Epigenetics 450K DNA methylation APrON study |
| url | http://www.sciencedirect.com/science/article/pii/S016041202200109X |
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