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DNA methylation at GRIN2B partially mediates the association between prenatal bisphenol F exposure and cognitive functions in 7-year-old children in the SELMA study
Uppsala University.
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013).ORCID iD: 0000-0002-4330-9193
Karlstad University, Faculty of Health, Science and Technology (starting 2013), Department of Health Sciences (from 2013). Univ New South Wales, Sch Psychiat, Sydney, NSW, Australia; South Western Sydney Local Hlth Dist, Liverpool, Australia.ORCID iD: 0000-0002-9739-7184
Karolinska institute; Canadian Neurol Ctr, Mississauga, ON, Canada.
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2021 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 156, article id 106617Article in journal (Refereed) Published
Abstract [en]

Background: Accumulating evidence suggests that prenatal chemical exposure triggers epigenetic modifications that could influence health outcomes later in life. In this study, we investigated whether DNA methylation (DNAm) levels at the glutamate ionotropic receptor NMDA type subunit 2B (GRIN2B) gene underlies the association between prenatal exposure to an endocrine disrupting chemical (EDC), bisphenol F (BPF), and lower cognitive functions in 7-year-old children. Methods: Data from 799 children participating in the Swedish Environmental Longitudinal Mother and child Asthma and allergy (SELMA) pregnancy cohort was analyzed. Prenatal BPF exposure was assessed by measuring BPF levels in maternal urine. At age 7, DNAm of three CpG sites in a regulatory region of the GRIN2B gene was analyzed from buccal swabs using bisulfite-Pyrosequencing. Cognitive functions, including full-scale IQ and four subscales, were evaluated using the Wechsler Intelligence Scale for Children (WISC-IV). Associations between prenatal BPF exposure and GRIN2B DNAm, as well as between GRIN2B DNAm and cognitive functions, were determined using regression models adjusted for potential confounders. Generalized structural equation models (gSEM) were used to evaluate if GRIN2B DNAm mediates the association between prenatal BPF exposure and cognitive functions at 7 years of age. Results: Prenatal BPF exposure was positively associated with GRIN2B DNAm levels at the third CpG site (CpG3), while CpG3 methylation was inversely associated with cognitive test scores. Mediation analyses showed that CpG3 methylation exerted 6–9% of the association between BPF exposure and full-scale IQ, as well as verbal comprehension and perceptual reasoning in boys, while not significant in girls. Conclusions: This study is the first to identify locus-specific DNAm as a mediating factor underlying an epidemiological association between prenatal EDC exposure and cognitive functions in childhood. It also confirms previous findings, that GRIN2B DNAm is responsive to environmental exposures.

Place, publisher, year, edition, pages
Elsevier, 2021. Vol. 156, article id 106617
Keywords [en]
Bisphenol F, BPF, Cognition, DNA methylation, EDCs, GRIN2B, Alkylation, Brain, Chemical modification, Endocrine disrupters, Genes, Methylation, Phenols, Regression analysis, Chemical exposure, Cognitive functions, EDC, Endocrine disrupting chemicals, Swedishs, DNA, endocrine disruptor, n methyl dextro aspartic acid receptor 2B, unclassified drug, child health, pollution exposure, pregnancy, Article, bisulfite pyrosequencing, buccal swab, child, cognitive defect, cohort analysis, CpG island, environmental exposure, experimental cognitive test, female, full scale IQ score, gene control, gene locus, GRIN2B gene, human, longitudinal study, male, prenatal exposure, priority journal, reasoning, school child, scoring system, sex difference, structural equation modeling, Swedish citizen, urine level, verbal communication, Wechsler intelligence scale for children
National Category
Health Sciences
Research subject
Public Health Science
Identifiers
URN: urn:nbn:se:kau:diva-85330DOI: 10.1016/j.envint.2021.106617ISI: 000685626800007Scopus ID: 2-s2.0-85106252162OAI: oai:DiVA.org:kau-85330DiVA, id: diva2:1577487
Available from: 2021-07-02 Created: 2021-07-02 Last updated: 2022-03-17Bibliographically approved

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Svensson, KatherineLin, Ping-IBornehag, Carl-Gustaf

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