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. 2019 May 16;11(1):80.
doi: 10.1186/s13148-019-0680-7.

DNA methylation changes related to nutritional deprivation: a genome-wide analysis of population and in vitro data

Yujie He  1   2 , Lot D de Witte  1   3 , Lotte C Houtepen  1 , Danny M Nispeling  1 , Zhida Xu  1 , Qiong Yu  4 , Yaqin Yu  4 , Elly M Hol  2   5 , René S Kahn  1   3 , Marco P Boks  6
Affiliations

DNA methylation changes related to nutritional deprivation: a genome-wide analysis of population and in vitro data

Yujie He et al. Clin Epigenetics. .

Abstract

Background: DNA methylation has recently been identified as a mediator between in utero famine exposure and a range of metabolic and psychiatric traits. However, genome-wide analyses are scarce and cross-sectional analyses are hampered by many potential confounding factors. Moreover, causal relations are hard to identify due to the lack of controlled experimental designs. In the current study, we therefore combined a comprehensive assessment of genome-wide DNA methylation differences in people exposed to the great Chinese famine in utero with an in vitro study in which we deprived fibroblasts of nutrition.

Methods: We compared whole blood DNA methylation differences between 25 individuals in utero exposed to famine and 54 healthy control individuals using the HumanMethylation450 platform. In vitro, we analyzed DNA methylation changes in 10 fibroblast cultures that were nutritionally deprived for 72 h by withholding fetal bovine serum.

Results: We identified three differentially methylated regions (DMRs) in four genes (ENO2, ZNF226, CCDC51, and TMA7) that were related to famine exposure in both analyses. Pathway analysis with data from both Chinese famine samples and fibroblasts highlighted the nervous system and neurogenesis pathways as the most affected by nutritional deprivation.

Conclusions: The combination of cross-sectional and experimental data provides indications that biological adaptation to famine leads to DNA methylation changes in genes involved in the central nervous system.

Keywords: Chinese famine; Genome-wide DNA methylation; Nutrition deprivation; Pathway analysis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Significant pathway analysis based on CpGs (2706) associated with famine in both the Chinese famine and fibroblast study. a Significant pathways from GO analysis. Pathways in red represent molecular functions, in green represent cellular components, and in blue represent biological processes. X-axis displays the minus log p value of the association with the SetRank value of the gene set. b Significant pathway analysis from Reactome and WikiPathways. Reactome pathway is in purple, and WikiPathways is in orange. X-axis displays the minus log p value of association with the SetRank value of the gene set
See this image and copyright information in PMC

References

    1. Schübeler D. Function and information content of DNA methylation. Nature. 2015;517:321–326. doi: 10.1038/nature14192. - DOI - PubMed
    1. Cho CE, Pannia E, Huot PSP, Sánchez-Hernández D, Kubant R, Dodington DW, et al. Methyl vitamins contribute to obesogenic effects of a high multivitamin gestational diet and epigenetic alterations in hypothalamic feeding pathways in Wistar rat offspring. Mol Nutr Food Res. 2015;59:476–489. doi: 10.1002/mnfr.201400663. - DOI - PubMed
    1. Heijmans BT, Tobi EW, Stein AD, Putter H, Blauw GJ, Susser ES, et al. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc Natl Acad Sci U S A. 2008;105:17046–17049. doi: 10.1073/pnas.0806560105. - DOI - PMC - PubMed
    1. Finer S, Iqbal MS, Lowe R, Ogunkolade BW, Pervin S, Mathews C, et al. Is famine exposure during developmental life in rural Bangladesh associated with a metabolic and epigenetic signature in young adulthood? A historical cohort study. BMJ Open. 2016;6:e011768. doi: 10.1136/bmjopen-2016-011768. - DOI - PMC - PubMed
    1. Huang C, Li Z, Wang M, Martorell R. Early Life Exposure to the 1959-1961 Chinese famine has long-term health consequences. J Nutr. 2010;140:1874–1878. doi: 10.3945/jn.110.121293. - DOI - PubMed

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