Prenatal gestational diabetes mellitus exposure and accelerated offspring DNA methylation age in early childhood

ABSTRACT

Background: We investigated the association between prenatal GDM exposure and offspring DNA methylation (DNAm) age at 3–10 years of age in the Tianjin GDM Observational Study.

Methods: This study included 578 GDM and 578 non-GDM mother-child pairs. Children underwent an exam with anthropometric measurements and blood draw for DNAm analysis (Illumina 850 K array) at a median age of 5.9 years (range 3.1–10.2). DNAm age was calculated using two epigenetic clock algorithms (Horvath and Hannum). The residual resulting from regressing DNAm age on chronological age was used as a metric for age acceleration.

Results: Chronological age was positively correlated with Horvath DNAm age (r = 0.53, p < 0.0001) and Hannum DNAm age (r = 0.38, p < 0.0001). Offspring age acceleration was higher in the GDM group than non-GDM group after adjustment for potential confounders (Horvath: 4.96 months higher, adjusted for sex, pre-pregnancy BMI, cell-type proportions, and technical bias, p = 0.0002; Hannum: 11.2 months higher, adjusted for cell-type proportions and technical bias, p < 0.0001). Increased offspring DNAm age acceleration was associated with increased offspring weight-for-age Z-score, BMI-for-age-Z-score, waist circumference, body fat percentage, subscapular skinfold, suprailiac skinfold, upper-arm circumference, and blood pressure; findings were stronger in the GDM group.

Conclusions: We found that offspring of women with GDM exhibit accelerated epigenetic age compared to control participants, independent of other maternal factors. Epigenetic age in offspring was associated with cardiometabolic risk factors, suggesting that GDM and GDM-associated factors may have long-term effects on offspring epigenetic age and contribute to health outcomes.

KEYWORDS:

• Gestational diabetes mellitus
• DNA methylation
• epigenetic age

Availability of data and materials

The datasets generated and/or analysed during the current study are not publicly available due to protection of individual privacy but are available from the corresponding author on reasonable request.

Authors’ contributions

GH designed the study. LW, HL, WL, JL, RG conducted the field research. GH, LH, and AAB designed and obtained funding for the DNA methylation study. SS, BJ, AD, YZ, YS conducted data organization and analysis. SS drafted the manuscript. All authors provided critical revisions to the manuscript and approved the final manuscript.

Consent for publication

Not applicable for this study.

Disclosure statement

The authors declare that they have no competing interests.

Ethics approval and consent to participate

Written informed consent was collected from all participants and this study was approved by the Human Subjects Committee of Tianjin Women’s and Children’s Health Center and the Institutional Review Boards of Columbia University Medical Center and Pennington Biomedical Research Center.

Additional information

Funding

This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK100790).