Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jun 29;15(1):107.
doi: 10.1186/s13148-023-01524-7.

Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age

Amélie Taschereau #  1 , Kathrine Thibeault #  1 , Catherine Allard  2 , Diana Juvinao-Quintero  3 , Patrice Perron  2   4 , Sharon M Lutz #  5   6 , Luigi Bouchard #  7   8   9 , Marie-France Hivert #  5   10
Affiliations

Maternal glycemia in pregnancy is longitudinally associated with blood DNAm variation at the FSD1L gene from birth to 5 years of age

Amélie Taschereau et al. Clin Epigenetics. .

Abstract

Background: In utero exposure to maternal hyperglycemia has been associated with an increased risk for the development of chronic diseases in later life. These predispositions may be programmed by fetal DNA methylation (DNAm) changes that persist postnatally. However, although some studies have associated fetal exposure to gestational hyperglycemia with DNAm variations at birth, and metabolic phenotypes in childhood, no study has yet examined how maternal hyperglycemia during pregnancy may be associated with offspring DNAm from birth to five years of age.

Hypothesis: Maternal hyperglycemia is associated with variation in offspring DNAm from birth to 5 years of age.

Methods: We estimated maternal hyperglycemia using the area under the curve for glucose (AUCglu) following an oral glucose tolerance test conducted at 24-30 weeks of pregnancy. We quantified DNAm levels in cord blood (n = 440) and peripheral blood at five years of age (n = 293) using the Infinium MethylationEPIC BeadChip (Illumina). Our total sample included 539 unique dyads (mother-child) with 194 dyads having DNAm at both time-points. We first regressed DNAm M-values against the cell types and child age for each time-point separately to account for the difference by time of measurement for these variables. We then used a random intercept model from the linear mixed model (LMM) framework to assess the longitudinal association between maternal AUCglu and the repeated measures of residuals of DNAm. We adjusted for the following covariates as fixed effects in the random intercept model: maternal age, gravidity, smoking status, child sex, maternal body mass index (BMI) (measured at first trimester of pregnancy), and a binary variable for time-point.

Results: In utero exposure to higher maternal AUCglu was associated with lower offspring blood DNAm levels at cg00967989 located in FSD1L gene (β = - 0.0267, P = 2.13 × 10-8) in adjusted linear regression mixed models. Our study also reports other CpG sites for which DNAm levels were suggestively associated (P < 1.0 × 10-5) with in utero exposure to gestational hyperglycemia. Two of these (cg12140144 and cg07946633) were found in the promotor region of PRDM16 gene (β: - 0.0251, P = 4.37 × 10-07 and β: - 0.0206, P = 2.24 × 10-06, respectively).

Conclusion: Maternal hyperglycemia is associated with offspring DNAm longitudinally assessed from birth to 5 years of age.

Keywords: DNAm; Epigenetics; Fetal programming; Gestational hyperglycemia; Offspring; Pregnancy.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart illustrating the participant selection from the Gen3G prospective cohort
Fig. 2
Fig. 2
Epigenome-wide association plot (− log10 P-values) for maternal AUCglu. Manhattan plot for the EWAS of maternal AUCglu following a 75 g-OGTT with DNAm measured longitudinally at birth and five years of age (red line: Bonferroni threshold = P-value < 6.9 × 10–8; blue line: Suggestive threshold = P < 1.0 × 10–5)
Fig. 3
Fig. 3
FSD1L and PRDM16 gene regional plot association (− log10 P-values) for maternal AUCglu. Genomic regional plots for a FSD1L (on Chr 9) and b PRDM16 (on Chr 1) genes of maternal AUCglu following a 75 g-OGTT with DNAm measured longitudinally at birth and five years of age (Solid line: Bonferroni threshold = P-value < 6.9 × 10–8; dashed line: Suggestive threshold = P < 1.0 × 10–5)
Fig. 4
Fig. 4
Venn diagram showing common CpGs between maternal AUCglu, fasting, 1 h and 2 h post-OGTT glucose levels. All CpG sites shown in the Venn diagram were at least suggestively associated (P < 1.0 × 10–5) with maternal glucose measurements. Cg00967989 is located at the FSD1L gene locus; cg12140144 and cg07946633 are located at the PRDM16 gene locus
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Quintanilla Rodriguez BS, Mahdy H. Gestational Diabetes. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 17]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK545196/ - PubMed
    1. Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF diabetes atlas: estimation of global and regional gestational diabetes mellitus prevalence for 2021 by international association of diabetes in pregnancy study group’s criteria. Diabetes Res Clin Pract. 2022;183:109050. doi: 10.1016/j.diabres.2021.109050. - DOI - PubMed
    1. Pu J, Zhao B, Wang EJ, Nimbal V, Osmundson S, Kunz L, et al. Racial/ethnic differences in gestational diabetes prevalence and contribution of common risk factors: racial/ethnic differences in GDM risk factors. Paediatr Perinat Epidemiol. 2015;29(5):436–443. doi: 10.1111/ppe.12209. - DOI - PMC - PubMed
    1. Gupta Y, Kalra B. Screening and diagnosis of gestational diabetes mellitus. JPMA J Pak Med Assoc. 2016;66(9 Suppl 1):S19–21. - PubMed
    1. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008;358(19):1991–2002. - PubMed

Publication types

Substances