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Session: Diet, Body Size, and Diabetes in Pregnancy: Impact on Offspring Metabolic Health (Oral 12)

(OR12-02-23) Offspring DNA Methylation of Metabolic Genes at Birth Associates With Maternal Folate and Choline Intake and Offspring Adiposity in Infancy and Childhood

Sunday, July 23, 2023

4:12 PM – 4:24 PM ET

Location: Constitution A

Presenting Author(s)

Stephanie W. Waldrop, MD, MPH (she/her/hers)

Fellow
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States

Disclosure(s): No relevant financial relationship(s) with ineligible companies to disclose.

Co-Author(s)

Sarah J. Borengasser, PhD (she/her/hers)

Associate Professor
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
DD

Dana Dabelea, MD, PhD

University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
KK

Katerina Kechris, PhD

University of Colorado Anschutz Medical Campus
SN

Sierra Niemiec, MS

University of Colorado Anschutz Medical Campus
WP

Wei Perng, PhD

University of Colorado Denver Anschutz Medical Campus
Aurora, Colorado, United States
Katherine A. Sauder, PhD

Assistant Professor
University of Colorado Anschutz Medical Campus
Aurora, Colorado, United States
AS

Anne Starling, PhD

University of Colorado Anschutz Medical Campus
IY

Ivana V. Yang, PhD

University of Colorado Anschutz Medical Campus

Disclosure(s):

Stephanie W. Waldrop, MD, MPH: No relevant financial relationship(s) with ineligible companies to disclose.

Sarah J. Borengasser, PhD: No relevant financial relationship(s) with ineligible companies to disclose.

Objectives: To determine the effect of maternal excessive folate/folic acid (FoFa) and insufficient choline intake on offspring cord blood DNA methylation (DNAm) and infant adiposity among mother-infant dyads in which maternal mean intakes were outside recommended limits for pregnancy.

Methods: A subset of 586 dyads from the Healthy Start Study were followed from early pregnancy to early childhood. Maternal intake of vitamin B2, vitamin B6, vitamin B12, Fo/Fa and choline was assessed during pregnancy via 24-hour recalls and dietary supplement questionnaires. Cord blood DNAm was measured via the Infinium 450K. Using linear regression, we assessed if cord blood DNAm associated with maternal vitamin intake and found differentially methylated regions (DMRs) using comb-p. We identified the probe within each DMR most associated with offspring adiposity measured by PEAPOD® or BODPOD® at birth, infancy, and childhood. Maternal pre-pregnancy BMI, age, race, mean caloric intake, infant sex, gestational age at birth and cell composition were covariates. The Sidak correction was used for multiple comparisons.

Results: We found DMRs in 4 genes (SEPT8, FOXC2-AS1, LINC00533, DPPA5) significantly associated with maternal FoFa intake and offspring adiposity, and in 7 genes (CXorf38, TCEANC, TMEM232, DDX43, TNRC6C, KCNA3, BNIP3) significantly associated with choline intake and offspring adiposity. DNAm of DPPA5 (ß = 1.8) and FOXC2-AS1 (ß = 1.4) was associated with FoFa intake and offspring adiposity at birth. DNAm of DDX43 (ß =1.7) and KCNA3 (ß =1.5) was associated with choline intake and offspring adiposity at birth. TCEANC (ß= 1.1) and CXorf38 (ß = 1.0) were both associated with choline intake and offspring adiposity in infancy. These genes play roles in cell re-programming; intracellular trafficking; mitochondrial metabolism and triacylglycerol storage; and body weight regulation and insulin sensitivity.

Conclusions: Cord blood DNAm of DMRs in metabolic genes associates with maternal FoFa and choline intake and offspring adiposity measures at birth and infancy only, revealing potential biologically plausible epigenetic biomarkers linked to maternal nutrition.

Funding Sources: National Institutes of Health, National Institute of Diabetes, Digestive and Kidney Diseases