TY - JOUR
T1 - Prenatal multivitamin use and mthfr genotype are associated with newborn cord blood dna methylation
AU - Bakulski, Kelly M.
AU - Dou, John F.
AU - Feinberg, Jason I.
AU - Brieger, Katharine K.
AU - Croen, Lisa A.
AU - Hertz-Picciotto, Irva
AU - Newschaffer, Craig J.
AU - Schmidt, Rebecca J.
AU - Daniele Fallin, M.
N1 - Funding Information:
Funding: Funding for the EARLI study was provided by the National Institutes of Health (R01ES016443, PI: Newschaffer) and Autism Speaks (003953 PI: Newschaffer). The nutrient measures in this study were supported by the National Institutes of Health (R01 ES025574, PI: Schmidt). Support for this research was also provided by the National Institutes of Health (P30 ES017885). Mr. Dou and Dr. Bakulski were supported by grants from the National Institutes of Health (R01 ES025531, PI: Fallin; R01 AG055406, MPI: Bakulski; R01 AG067592, MPI: Bakulski; R01 MD013299). Dr. Brieger was supported by the Genome Sciences Training Program (T32 HG000040), the Medical Scientists Training Program (T32 GM007863), and the University of Michigan Department of Epidemiology David Schottenfeld, M.D. Endowed Scholarship. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2020/12/2
Y1 - 2020/12/2
N2 - Background: Fetal development involves cellular differentiation and epigenetic changes —complex processes that are sensitive to environmental factors. Maternal nutrient levels during pregnancy affect development, and methylene tetrahydrofolate reductase (MTHFR) is important for processing the nutrient folate. Hypothesis: We hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns. Methods: In the pregnancy cohort, Early Autism Risk Longitudinal Investigation (EARLI), health history, and genotype information was obtained (n = 249 families). Cord blood DNA methylation (n = 130) was measured using the Illumina HumanMethylation450k array and global DNA methylation levels were computed over 455,698 sites. Supplement use preconception and during pregnancy were surveyed at visits during pregnancy. We evaluated associations between maternal preconception supplement intake and global DNA methylation or DNA methylation density distributions of newborn cord blood, stratified by the presence of a variant maternal MTHFR C677T allele. Results: Maternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal MTHFR genotype (interaction term p = 0.013). For mothers without the MTHFR variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation (p = 0.04) and was also associated with the cumulative density distribution of methylation (p = 0.03). For mothers with at least one variant allele, multivitamin intake had a null −0.06% (95% CI: −0.45, 0.33) association with global cord blood DNA methylation, and was not associated with the cumulative density distribution (p = 0.37). Conclusions: We observed that cord blood DNA methylation was associated with maternal supplement exposure preconception and maternal genotype. Genetic context should be considered when assessing DNA methylation effects of modifiable risk factors around the time of pregnancy.
AB - Background: Fetal development involves cellular differentiation and epigenetic changes —complex processes that are sensitive to environmental factors. Maternal nutrient levels during pregnancy affect development, and methylene tetrahydrofolate reductase (MTHFR) is important for processing the nutrient folate. Hypothesis: We hypothesize that supplement intake before pregnancy and maternal genotype are associated with DNA methylation in newborns. Methods: In the pregnancy cohort, Early Autism Risk Longitudinal Investigation (EARLI), health history, and genotype information was obtained (n = 249 families). Cord blood DNA methylation (n = 130) was measured using the Illumina HumanMethylation450k array and global DNA methylation levels were computed over 455,698 sites. Supplement use preconception and during pregnancy were surveyed at visits during pregnancy. We evaluated associations between maternal preconception supplement intake and global DNA methylation or DNA methylation density distributions of newborn cord blood, stratified by the presence of a variant maternal MTHFR C677T allele. Results: Maternal preconceptional multivitamin intake was associated with cord blood methylation, dependent on maternal MTHFR genotype (interaction term p = 0.013). For mothers without the MTHFR variant allele, multivitamin intake was associated with 0.96% (95% CI: 0.09, 1.83) higher global cord blood methylation (p = 0.04) and was also associated with the cumulative density distribution of methylation (p = 0.03). For mothers with at least one variant allele, multivitamin intake had a null −0.06% (95% CI: −0.45, 0.33) association with global cord blood DNA methylation, and was not associated with the cumulative density distribution (p = 0.37). Conclusions: We observed that cord blood DNA methylation was associated with maternal supplement exposure preconception and maternal genotype. Genetic context should be considered when assessing DNA methylation effects of modifiable risk factors around the time of pregnancy.
KW - Cord blood
KW - DNA methylation
KW - MTHFR
KW - Multivitamin
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U2 - 10.3390/ijerph17249190
DO - 10.3390/ijerph17249190
M3 - Article
C2 - 33317014
AN - SCOPUS:85097536199
SN - 1661-7827
VL - 17
SP - 1
EP - 16
JO - International Journal of Environmental Research and Public Health
JF - International Journal of Environmental Research and Public Health
IS - 24
M1 - 9190
ER -