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Title: Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults
Authors: Chambers, John Campbell
Parmar, Priyanka
Lowry, Estelle
Cugliari, Giovanni
Suderman, Matthew
Wilson, Rory
Karhunen, Ville
Andrew, Toby
Wiklund, Petri
Wielscher, Matthias
Guarrera, Simonetta
Teumer, Alexander
Lehne, Benjamin
Milani, Lili
de Klein, Niek
Mishra, Pashupati P.
Melton, Phillip E.
Mandaviya, Pooja R.
Kasela, Silva
Nano, Jana
Zhang, Weihua
Zhang, Yan
Mori, Trevor A.
Bonnefond, Amelie
Uitterlinden, Andre G.
Peters, Annette
Schöttker, Ben
Gieger, Christian
Anderson, Denise
Boomsma, Dorret I.
Grabe, Hans J.
Panico, Salvatore
Veldink, Jan H.
van Meurs, Joyce B.J.
van den Berg, Leonard
Heijmans, Bastiaan T.
Muka, Taulant
Kooner, Jaspal S.
Fischer, Krista
Waldenberger, Melanie
Beilin, Lawrence J.
Franke, Lude
Loh, Marie
van Greevenbroek, Marleen M.J.
Nauck, Matthias
Kähönen, Mika
Hurme, Mikko A.
Raitakari, Olli T.
Franco, Oscar H.
Slagboom, P.Eline
van der Harst, Pim
Kunze, Sonja
Felix, Stephan B.
Zhang, Tao
Chen, Wei
Froguel, Philippe
Huang, Rae-Chi
Lehtimäki, Terho
Rathmann, Wolfgang
Relton, Caroline L.
Matullo, Giuseppe
Brenner, Hermann
Verweij, Niek
Li, Shengxu
Järvelin, Marjo-Riitta
Sebert, Sylvain
Issue Date: 2018
Source: Parmar, P., Lowry, E., Cugliari, G., Suderman, M., Wilson, R., Karhunen, V., . . . Sebert, S. (2018). Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults. EBioMedicine, 38, 206-216. doi:10.1016/j.ebiom.2018.10.066
Series/Report no.: EBioMedicine
Abstract: Background: DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. Methods: We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL—C), triglycerides (TG), diastolic, and systolic blood pressure (BP). Findings: Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10−7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10−8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. Interpretation: Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors.
ISSN: 2352-3964
DOI: 10.1016/j.ebiom.2018.10.066
Rights: © 2018 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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