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Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Periconceptional folate intake influences DNA methylation at birth based on dietary source in an analysis of
Eric M Nickels1,2, Shaobo Li2, Libby Morimoto3
1Children's Hospital Los Angeles, Center for Blood Disease Institute, Los Angeles, CA, USA.
Insights
Periconceptional folate intake from food and supplements influences infant DNA methylation, with variations observed based on folate source and acute lymphoblastic leukemia (ALL) status. Hispanic individuals with lower socioeconomic status showed a unique response to folic acid supplementation.
Area of Science:
- Epigenetics
- Nutritional Epidemiology
- Pediatric Oncology
Background:
- Periconceptional folate intake is linked to offspring DNA methylation establishment.
- The influence of folate source (food vs. supplements) on this relationship is unclear.
- Maternal folate intake is associated with reduced pediatric acute lymphoblastic leukemia (ALL) risk, but the underlying mechanism remains unknown.
Purpose of the Study:
- To investigate the association between periconceptional folate intake by source and DNA methylation at birth.
- To explore variations in this association by pediatric ALL case status.
- To examine the role of folate source in the context of pediatric leukemia risk and epigenetics.
Main Methods:
- Epigenome-wide association study (EWAS) using neonatal blood spots from pediatric ALL cases and controls.
- Comparison of genome-wide DNA methylation with periconceptional folate intake from total, food, and supplemental sources.
- Multivariable linear regression and interaction term analysis to evaluate differential methylation responses by ALL status, socioeconomic factors, and ethnicity.
Main Results:
- Two differentially methylated probes (DMPs) associated with food and supplemental folate intake were identified.
- The DUSP22 promoter region showed DNA hypermethylation in ALL cases in response to total and food folate.
- Eight interaction term DMPs indicated variable methylation responses to folate by ALL case status, with supplemental folic acid showing a notable association in lower socioeconomic Hispanic subjects.
Conclusions:
- Modest associations exist between periconceptional folate intake and DNA methylation, with variations by folate source and ALL case status.
- Hispanic individuals with lower income and education levels demonstrate a distinct responsiveness to periconceptional folate supplementation.
- These findings highlight the importance of folate source and socioeconomic factors in folate's epigenetic effects and potential role in pediatric leukemia.
Background:
Periconceptional folate intake is associated with the establishment of DNA methylation in offspring; however, variations in this relation by food sources compared with folic acid supplements are not described. Also, maternal folate intake is associated with decreased risk of pediatric acute lymphoblastic leukemia (ALL), but the mechanism is not known.
Objectives:
We evaluated the relation between periconceptional folate intake by source and DNA methylation at birth in a cohort of pediatric ALL cases and controls in an epigenome-wide association study.
Methods:
Genome-wide DNA methylation status obtained from archived neonatal blood spots from pediatric ALL cases (n = 189) and controls (n = 205) in the California Childhood Leukemia Study (CCLS) from 1995-2008 was compared with periconceptional folate from total, food, and supplemental sources using multivariable linear regression. Further stratification was performed by income, education, ethnicity, and total folate intake. We evaluated variable DNA methylation response to periconceptional folate by ALL case status through an interaction term.
Results:
Two significant differentially methylated probes (DMPs) were associated with food and supplemental periconceptional folate intake in all subjects (n = 394). The top differentially methylated region at the promoter region of DUSP22(dual specificity phosphatase 22) demonstrated DNA hypermethylation in ALL cases but not in controls in response to total and food folate intake. We further identified 8 interaction term DMPs with variable DNA methylation response to folate intake by ALL case status. Further stratification of the cohort by education and ethnicity revealed a substantially higher number of DMPs associated with supplemental folic acid intake in Hispanic subjects with lower income and educational level.
Conclusions:
We identified modest associations between periconceptional folate intake and DNA methylation differing by source, including variation by ALL case status. Hispanic subjects of lower income and education appear uniquely responsive to periconceptional folate supplementation.
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