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

被引：186

作者：

Joubert, Bonnie R. ^{[1
]}

den Dekker, Herman T. ^{[2
,3
,4
]}

Felix, Janine F. ^{[2
,4
,5
]}

Bohlin, Jon ^{[6
]}

Ligthart, Symen ^{[4
]}

Beckett, Emma ^{[7
,8
]}

Tiemeier, Henning ^{[4
,9
]}

van Meurs, Joyce B. ^{[10
]}

Uitterlinden, Andre G. ^{[4
,10
]}

Hofman, Albert ^{[4
]}

Haberg, Siri E. ^{[6
]}

Reese, Sarah E. ^{[1
]}

Peters, Marjolein J. ^{[10
]}

Andreassen, Bettina Kulle ^{[11
]}

Steegers, Eric A. P. ^{[12
]}

Nilsen, Roy M. ^{[13
]}

Vollset, Stein E. ^{[6
,14
]}

Midttun, Oivind ^{[15
]}

Ueland, Per M. ^{[16
,17
]}

Franco, Oscar H. ^{[4
]}

Dehghan, Abbas ^{[4
]}

de Jongste, Johan C. ^{[3
]}

Wu, Michael C. ^{[18
]}

Wang, Tianyuan ^{[1
]}

Peddada, Shyamal D. ^{[1
]}

Jaddoe, Vincent W. V. ^{[2
,4
,5
]}

Nystad, Wenche ^{[6
]}

Duijts, Liesbeth ^{[2
,3
,4
]}

London, Stephanie J. ^{[1
]}

机构：

[1] NIEHS, Div Intramural Res, NIH, POB 12233, Res Triangle Pk, NC 27709 USA

[2] Univ Med Ctr Rotterdam, Generat R Study Grp, Erasmus MC, NL-3000 CA Rotterdam, Netherlands

[3] Univ Med Ctr Rotterdam, Div Resp Med, Erasmus MC, Dept Pediat, NL-3000 CA Rotterdam, Netherlands

[4] Univ Med Ctr Rotterdam, Dept Epidemiol, Erasmus MC, NL-3000 CA Rotterdam, Netherlands

[5] Univ Med Ctr Rotterdam, Dept Pediat, Erasmus MC, NL-3000 CA Rotterdam, Netherlands

[6] Norwegian Inst Publ Hlth, N-0403 Oslo, Norway

[7] Univ Newcastle, Sch Environm & Life Sci, Dept Appl Sci, Ourimbah, NSW 2258, Australia

[8] CSIRO, Food & Nutr Flagship, N Ryde, NSW 2113, Australia

[9] Univ Med Ctr Rotterdam, Erasmus MC, Dept Psychiat, NL-3000 CA Rotterdam, Netherlands

[10] Univ Med Ctr Rotterdam, Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands

[11] Univ Oslo, Inst Clin Med, Dept Clin Mol Biol, N-0316 Oslo, Norway

[12] Univ Med Ctr Rotterdam, Erasmus MC, Dept Obstet & Gynaecol, NL-3000 CA Rotterdam, Netherlands

[13] Haukeland Hosp, Dept Res & Dev, Clin Res Ctr, N-5021 Bergen, Norway

[14] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5018 Bergen, Norway

[15] Bevital AS, Laboratoriebygget, N-5018 Bergen, Norway

[16] Univ Bergen, Dept Clin Sci, N-5018 Bergen, Norway

[17] Haukeland Hosp, Lab Clin Biochem, N-5018 Bergen, Norway

[18] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Program, Seattle, WA 98109 USA

来源：

NATURE COMMUNICATIONS | 2016年 / 7卷

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

FOLIC-ACID SUPPLEMENTATION; COPY NUMBER VARIATIONS; NORWEGIAN MOTHER; CHILD COHORT; DISCOVERY; APC2; HOMOCYSTEINE; ASSOCIATION; PREGNANCY; RESOURCE;

D O I：

10.1038/ncomms10577

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

共 50 条

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