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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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Record number 534521
Title DNA methylation as a mediator of the association between prenatal adversity and risk factors for metabolic disease in adulthood
Author(s) Tobi, Elmar W.; Slieker, Roderick C.; Luijk, René; Dekkers, Koen F.; Stein, Aryeh D.; Xu, Kate M.; Slagboom, P.E.; Zwet, Erik W. Van; Lumey, L.H.; Heijmans, Bastiaan T.; T'Hoen, Peter A.; Pool, René; Greevenbroek, Marleen M. Van; Stehouwer, Coen D.; Kallen, Carla J. Van Der; Schalkwijk, Casper G.; Wijmenga, Cisca; Zhernakova, Sasha; Tigchelaar, Ettje F.; Beekman, Marian; Deelen, Joris; Heemst, Diana Van; Veldink, Jan H.; Berg, Leonard H. Van Den; Duijn, Cornelia M. Van; Hofman, Albert; Uitterlinden, André G.; Jhamai, P.M.; Verbiest, Michael; Verkerk, Marijn; Breggen, Ruud Van Der; Rooij, Jeroen Van; Lakenberg, Nico; Mei, Hailiang; Bot, Jan; Zhernakova, Dasha V.; Hof, Peter Van 't; Deelen, Patrick; Nooren, Irene; Moed, Matthijs; Vermaat, Martijn; Jan Bonder, Marc; Dijk, Freerk Van; Arindrarto, Wibowo; Kielbasa, Szymon M.; Swertz, Morris A.; Isaacs, Aaron; Franke, Lude
Source Science Advances 4 (2018)1. - ISSN 2375-2548
Department(s) Global Nutrition
Publication type Refereed Article in a scientific journal
Publication year 2018
Abstract Although it is assumed that epigenetic mechanisms, such as changes in DNA methylation (DNAm), underlie the relationship between adverse intrauterine conditions and adult metabolic health, evidence from human studies remains scarce. Therefore, we evaluated whether DNAm in whole blood mediated the association between prenatal famine exposure and metabolic health in 422 individuals exposed to famine in utero and 463 (sibling) controls. We implemented a two-step analysis, namely, a genome-wide exploration across 342, 596 cytosine-phosphate-guanine dinucleotides (CpGs) for potential mediators of the association between prenatal famine exposure and adult body mass index (BMI), serum triglycerides (TG), or glucose concentrations, which was followed by formalmediation analysis.DNAm mediated the association of prenatal famine exposure with adult BMI and TG but not with glucose. DNAm at PIM3 (cg09349128), a gene involved in energy metabolism, mediated 13.4% [95% confidence interval (CI), 5 to 28%] of the association between famine exposure and BMI. DNAm at six CpGs, including TXNIP (cg19693031), influencing b cell function, and ABCG1 (cg07397296), affecting lipid metabolism, together mediated 80% (95% CI, 38.5 to 100%) of the association between famine exposure and TG. Analyses restricted to those exposed to famine during early gestation identified additional CpGs mediating the relationship with TG near PFKFB3 (glycolysis) and METTL8 (adipogenesis). DNAm at the CpGs involved was associated with gene expression in an external data set and correlated with DNAm levels in fat depots in additional postmortem data. Our data are consistent with the hypothesis that epigenetic mechanisms mediate the influence of transient adverse environmental factors in early life on long-termmetabolic health. The specific mechanism awaits elucidation.
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