25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC)

25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC)
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DOI:
10.1016/j.jsbmb.2016.03.005
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发表时间:
2016-05-01
影响因子:
4.1
通讯作者:
Nystad, W.
Nystad, W.
中科院分区:
生物学2区
文献类型:
--
作者:
Suderman, M.;Stene, L. C.;Nystad, W.

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该研究的目的是调查孕中期孕妇是否服用25-羟基维生素。D浓度与脐带血DNA甲基化有关。DNA甲基化检测采用Illumina Human Metylation450 BeadChip,对参与挪威母婴队列(MOBA)的819对母亲/新生儿和参与雅芳亲子纵向研究(ALSPAC)的597对母亲/新生儿进行了检测。在脐带血DNA中的473,731个CpG DNA甲基化位点中,在调整多项测试(错误发现率(FDR)和GT;0.5;473,731个测试)后,没有一个与母亲25-羟基维生素D密切相关。对两个队列的结果进行荟萃分析,使用Fisher方法合并p值,也没有加强研究结果(FDR>0.2)。对四个先验确定的候选基因(CYP24A1、CYP27B1、CYP27A1和CYP2R1)附近的一组CpG位点的进一步探索没有发现任何与FDR<0.05(56项测试)相关的结果。在这项关于母亲维生素D状态对DNA甲基化的潜在影响的大型全基因组评估中,我们没有在1416名新生儿中发现任何令人信服的关联。如果真的存在关联,识别它们可能需要更大规模的联合研究、扩大基因组覆盖范围、调查替代细胞类型或在不同的妊娠时间点测量25-羟基维生素D。(C)2016年提交人。爱思唯尔有限公司出版。
The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin. D concentrations are associated with cord blood DNA methylation.DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC).Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR) > 0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR> 0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR < 0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points. (C) 2016 The Authors. Published by Elsevier Ltd.