PMID- 34015668
OWN - NLM
STAT- MEDLINE
DCOM- 20210902
LR  - 20210902
IS  - 1873-6750 (Electronic)
IS  - 0160-4120 (Linking)
VI  - 156
DP  - 2021 Nov
TI  - 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.
PG  - 106617
LID - S0160-4120(21)00242-7 [pii]
LID - 10.1016/j.envint.2021.106617 [doi]
AB  - 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.
CI  - Copyright (c) 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Engdahl, Elin
AU  - Engdahl E
AD  - Uppsala University, Department of Organismal Biology, 752 36 Uppsala, Sweden. 
      Electronic address: elin.engdahl@ebc.uu.se.
FAU - Svensson, Katherine
AU  - Svensson K
AD  - Karlstad University, Department of Health Sciences, 651 88 Karlstad, Sweden.
FAU - Lin, Ping-I Daniel
AU  - Lin PD
AD  - Karlstad University, Department of Health Sciences, 651 88 Karlstad, Sweden.
FAU - Alavian-Ghavanini, Ali
AU  - Alavian-Ghavanini A
AD  - Karolinska Institutet, Swetox, Unit of Toxicology Sciences, 151 36 Sodertalje, 
      Sweden.
FAU - Lindh, Christian
AU  - Lindh C
AD  - Lund University, Division of Occupational and Environmental Medicine, 223 81 
      Lund, Sweden.
FAU - Ruegg, Joelle
AU  - Ruegg J
AD  - Uppsala University, Department of Organismal Biology, 752 36 Uppsala, Sweden; 
      Karlstad University, Department of Health Sciences, 651 88 Karlstad, Sweden.
FAU - Bornehag, Carl-Gustaf
AU  - Bornehag CG
AD  - Karlstad University, Department of Health Sciences, 651 88 Karlstad, Sweden; 
      Icahn School of Medicine at Mount Sinai, NY 10029, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210518
PL  - Netherlands
TA  - Environ Int
JT  - Environment international
JID - 7807270
RN  - 0 (Benzhydryl Compounds)
RN  - 0 (Phenols)
RN  - 0 (bisphenol F)
SB  - IM
MH  - *Asthma
MH  - Benzhydryl Compounds
MH  - Child
MH  - Cognition
MH  - DNA Methylation
MH  - Female
MH  - Humans
MH  - *Hypersensitivity
MH  - Male
MH  - Phenols
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects/genetics
MH  - Sweden
OTO - NOTNLM
OT  - BPF
OT  - Bisphenol F
OT  - Cognition
OT  - DNA methylation
OT  - EDCs
OT  - GRIN2B
EDAT- 2021/05/21 06:00
MHDA- 2021/09/03 06:00
CRDT- 2021/05/20 20:22
PHST- 2020/11/04 00:00 [received]
PHST- 2021/04/28 00:00 [revised]
PHST- 2021/04/30 00:00 [accepted]
PHST- 2021/05/21 06:00 [pubmed]
PHST- 2021/09/03 06:00 [medline]
PHST- 2021/05/20 20:22 [entrez]
AID - S0160-4120(21)00242-7 [pii]
AID - 10.1016/j.envint.2021.106617 [doi]
PST - ppublish
SO  - Environ Int. 2021 Nov;156:106617. doi: 10.1016/j.envint.2021.106617. Epub 2021 
      May 18.