Journal Article

Maternal plasma folate impacts differential DNA methylation in an epigenome-wide meta-analysis of newborns

Hofman, Albert, London, Stephanie J., Wang, Tianyuan, Duijts, Liesbeth, de Jongste, Johan C., Dehghan, Abbas, Peters, Marjolein J., Wu, Michael C., Håberg, Siri E., van Meurs, Joyce B., Beckett, Emma, Steegers, Eric A. P., Midttun, Øivind, Bohlin, Jon, Vollset, Stein E., Ueland, Per M., Reese, Sarah E., Kulle Andreassen, Bettina, den Dekker, Herman T., Ligthart, Symen, Peddada, Shyamal D., Tiemeier, Henning, Uitterlinden, Andre G., Nystad, Wenche, Jaddoe, Vincent W. V., Franco, Oscar H., Nilsen, Roy M., Joubert, Bonnie R., Felix, Janine F.

2016

Overview

Folate is vital for fetal development. Periconceptional folic acid supplementation and food fortification are recommended to prevent neural tube defects. Mechanisms whereby periconceptional folate influences normal development and disease are poorly understood: epigenetics may be involved. We examine the association between maternal plasma folate during pregnancy and epigenome-wide DNA methylation using Illumina’s HumanMethyl450 Beadchip in 1,988 newborns from two European cohorts. Here we report the combined covariate-adjusted results using meta-analysis and employ pathway and gene expression analyses. Four-hundred forty-three CpGs (320 genes) are significantly associated with maternal plasma folate levels during pregnancy (false discovery rate 5%); 48 are significant after Bonferroni correction. Most genes are not known for folate biology, including APC2 , GRM8 , SLC16A12 , OPCML , PRPH , LHX1 , KLK4 and PRSS21. Some relate to birth defects other than neural tube defects, neurological functions or varied aspects of embryonic development. These findings may inform how maternal folate impacts the developing epigenome and health outcomes in offspring. Folic acid is routinely recommended for women trying to conceive to ensure proper fetal development. Here, the authors perform a large epigenomics study to examine which fetal epigenetic changes are associated with varied maternal plasma folate levels.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/43 / 38/61 / 631/136 / 631/208/176/1988 / Acids / Adult / Birth defects / Cell Adhesion Molecules - genetics / Cytoskeletal Proteins - genetics / Deoxyribonucleic acid / DNA / DNA Methylation / Embryonic growth stage / Epigenesis, Genetic / Epigenetics / Female / Folic acid / Folic Acid - blood / Food / Food supply / Gene expression / Gene Expression Regulation, Developmental / GPI-Linked Proteins - genetics / Health sciences / Humanities and Social Sciences / Humans / Infant, Newborn / Kallikreins - genetics / LIM-Homeodomain Proteins - genetics / Medical research / Meta-analysis / Monocarboxylic Acid Transporters - genetics / multidisciplinary / Offspring / Pediatrics / Peripherins - genetics / Plasma / Pregnancy / Public health / R&D / Research & development / Science / Science (multidisciplinary) / Serine Endopeptidases - genetics / Transcription Factors - genetics / Vitamin B