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Cited by 38Maternal Mental Health During Pregnancy and PostpartumEpigenetics and DNA MethylationBirth, Development, and Health

Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1

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Vangeel, Elise Beau, Pishva, Ehsan, Hompes, Titia, van den Hove, Daniel, Lambrechts, Diether, Allegaert, Karel, Freson, Kathleen, Izzi, Benedetta +1 more·2017·Clinical Epigenetics
DOI 10.1186/s13148-017-0408-5PMC PMC5627482
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Abstract

There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach. We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER ( n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity. Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene ( GABBR1 ) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old. In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.

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  • Increased GABBR1 methylation in cord blood of male newborns was associated with increased cortisol levels in these infants on vaccination.

    “as well as increased cortisol levels in these infants on vaccination (applied stressor; Vangeel et al., 2017).”

    From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Vangeel et al., 2017

    The Results section reports that greater cord-blood GABBR1 methylation at CpG_1.2 was associated with a greater initial cortisol response to vaccination at four months. The paper identifies a male-specific association between pregnancy anxiety and GABBR1 methylation, but does not establish that the methylation–cortisol association was specific to male infants. No page numbers were available in our copy. (LLM, conf=0.88)

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  • In newborns of pregnant mothers who experienced anxiety measured by PRAQ, increased methylation of CpG islands of GABBR1 in cord blood of male newborns was associated with higher anxiety levels of pregnant mothers.

    “In newborns of pregnant mothers that experienced anxiety measured by PRAQ, a pregnancy-related anxiety questionnaire, researchers found that an increase in methylation of CpG islands of GABBR1 in the cord blood of male newborns (GABAB receptor subunit 1 gene), was associated with higher anxiety levels of pregnant mothers as well as increased cortisol levels in these infants on vaccination (applied”

    From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Vangeel et al., 2017

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References 65 · Cited by 38

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Authors
Vangeel, E. B., Pishva, E., Hompes, T., van den Hove, D., Lambrechts, D., Allegaert, K., Freson, K., Izzi, B., & Claes, S.
Affiliations
  • KU Leuven (BE)
  • University of Exeter (GB)
  • Erasmus MC - Sophia Children’s Hospital (NL)
  • Istituto Neurologico Mediterraneo (IT)
Corresponding author
Vangeel, Elise Beau
ORCID
Venue
Clinical Epigenetics
Publisher
Springer Science and Business Media LLC
Published
2017-10-03
Volume
9
Issue
1
Pages
107-107
ISSN
  • 1868-7075 (ISSN-L)
  • 1868-7083
DOI
10.1186/s13148-017-0408-5
PMC
PMC5627482
OpenAlex
W2762255589
Cited by
38
References
65
Citations by year
2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 10 · 2021: 5 · 2020: 5 · 2019: 7 · 2018: 2
FWCI
3.60
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Clinical Epigenetics (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (acceptedVersion, other-oa)
  • Lirias (submittedVersion, cc-by)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • RePub (Erasmus University Rotterdam) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Online Publication Service of Würzburg University (Würzburg University) (submittedVersion, cc-by)
  • Research Publications (Maastricht University) (submittedVersion, cc-by)
Funders
  • Fund for Scientific Research Flanders (FWO) (ELG-C5778-G.0A69.13, 12M2715N, 1800411N)
  • Deutsche Forschungsgemeinschaft (58/A5)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
prenatal anxiety, prenatal stress, DNA methylation, neonates, umbilical cord blood, GABBR1, GABAB receptors, differentially methylated regions, infant cortisol, hypothalamic-pituitary-adrenal axis, sex differences
MeSH terms
Anxiety, Female, Humans, Hydrocortisone, Infant, Infant, Newborn, Male, Pregnancy, Pregnancy Complications, Prenatal Exposure Delayed Effects, Vaccination, Receptors, GABA-B, DNA Methylation, Genetic Predisposition to Disease, Epigenesis, Genetic, Genome-Wide Association Study

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