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. 2024 Jan;32(1):187-199.
doi: 10.1002/oby.23915. Epub 2023 Oct 23.

Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity

Stephanie W Waldrop  1 , Sierra Niemiec  2 , Cheyret Wood  2 , Lauren E Gyllenhammer  3 , Thomas Jansson  4 , Jacob E Friedman  5 , Jeanie B Tryggestad  5 , Sarah J Borengasser  1 , Elizabeth J Davidson  6 , Ivana V Yang  6   7 , Katerina Kechris  2   7 , Dana Dabelea  7   8 , Kristen E Boyle  1   7
Affiliations

Cord blood DNA methylation of immune and lipid metabolism genes is associated with maternal triglycerides and child adiposity

Stephanie W Waldrop et al. Obesity (Silver Spring). 2024 Jan.

Abstract

Objective: Fetal exposures may impact offspring epigenetic signatures and adiposity. The authors hypothesized that maternal metabolic traits associate with cord blood DNA methylation, which, in turn, associates with child adiposity.

Methods: Fasting serum was obtained in 588 pregnant women (27-34 weeks' gestation), and insulin, glucose, high-density lipoprotein cholesterol, triglycerides, and free fatty acids were measured. Cord blood DNA methylation and child adiposity were measured at birth, 4-6 months, and 4-6 years. The association of maternal metabolic traits with DNA methylation (429,246 CpGs) for differentially methylated probes (DMPs) and regions (DMRs) was tested. The association of the first principal component of each DMR with child adiposity was tested, and mediation analysis was performed.

Results: Maternal triglycerides were associated with the most DMPs and DMRs of all traits tested (261 and 198, respectively, false discovery rate < 0.05). DMRs were near genes involved in immune function and lipid metabolism. Triglyceride-associated CpGs were associated with child adiposity at 4-6 months (32 CpGs) and 4-6 years (2 CpGs). One, near CD226, was observed at both timepoints, mediating 10% and 22% of the relationship between maternal triglycerides and child adiposity at 4-6 months and 4-6 years, respectively.

Conclusions: DNA methylation may play a role in the association of maternal triglycerides and child adiposity.

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Conflict of interest statement

Conflict of Interest: No potential conflicts of interest relevant to this article were reported.

Figures

Figure 1.
Figure 1.
Consort diagram of study participants and DNA methylation probes.
Figure 2.
Figure 2.. Epigenome wide analysis reveals DMR associations with maternal traits.
Data are Manhattan plots of CpGs, with DMRs highlighted in green, and number of DMRs with Šidák-adjusted P<0.05 with hypermethylation or hypomethylation at each chromosome for maternal insulin (A), glucose (B), HDL-C (C), Triglycerides (D), and FFA (E). Correlation among maternal traits and overlap among genes near DMRs (Šidák-adjusted P<0.05) for each trait are shown in a Venn Diagram (F).
Figure 3.
Figure 3.. Enrichment analyses reveal genes in metabolic, immunomodulatory, and adipogenic pathways
Top 20 Reactome Pathways from EnrichR enrichment analysis of genes near DMRs associated with each maternal trait at Šidák-adjusted P<0.10. Pathways are associated with maternal insulin (A), glucose (B), HDL-C (C), FFA (D), and triglycerides (E). Pathways are sorted by -log2 nominal p-value. Pathways with significant adjusted p-values are shown in red. Genes enriched in each pathway are shown. Genes near significant DMRs for each maternal trait (Šidák-adjusted P<0.05) are shown in blue text.
See this image and copyright information in PMC

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