TY - JOUR
T1 - Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults
AU - Parmar, Priyanka
AU - Lowry, Estelle
AU - Cugliari, Giovanni
AU - Suderman, Matthew
AU - Wilson, Rory
AU - Karhunen, Ville
AU - Andrew, Toby
AU - Wiklund, Petri
AU - Wielscher, Matthias
AU - Guarrera, Simonetta
AU - Teumer, Alexander
AU - Lehne, Benjamin
AU - Milani, Lili
AU - de Klein, Niek
AU - Mishra, Pashupati P.
AU - Melton, Phillip E.
AU - Mandaviya, Pooja R.
AU - Kasela, Silva
AU - Nano, Jana
AU - Zhang, Weihua
AU - Zhang, Yan
AU - Uitterlinden, Andre G.
AU - Peters, Annette
AU - Schöttker, Ben
AU - Gieger, Christian
AU - Anderson, Denise
AU - Boomsma, Dorret I.
AU - Grabe, Hans J.
AU - Panico, Salvatore
AU - Veldink, Jan H.
AU - van Meurs, Joyce B.J.
AU - van den Berg, Leonard
AU - Beilin, Lawrence J.
AU - Franke, Lude
AU - Loh, Marie
AU - van Greevenbroek, Marleen M.J.
AU - Nauck, Matthias
AU - Kähönen, Mika
AU - Hurme, Mikko A.
AU - Raitakari, Olli T.
AU - Franco, Oscar H.
AU - Slagboom, P. Eline
AU - van der Harst, Pim
AU - Kunze, Sonja
AU - Felix, Stephan B.
AU - Zhang, Tao
AU - Chen, Wei
AU - Mori, Trevor A.
AU - Bonnefond, Amelie
AU - Heijmans, Bastiaan T.
AU - Muka, Taulant
AU - Kooner, Jaspal S.
AU - Fischer, Krista
AU - Waldenberger, Melanie
AU - Froguel, Philippe
AU - Huang, Rae Chi
AU - Lehtimäki, Terho
AU - Rathmann, Wolfgang
AU - Relton, Caroline L.
AU - Matullo, Giuseppe
AU - Brenner, Hermann
AU - Verweij, Niek
AU - Li, Shengxu
AU - Chambers, John C.
AU - Järvelin, Marjo Riitta
AU - Sebert, Sylvain
AU - for the BIOS Consortium
AU - for the GLOBAL Meth QTL Consortium
N1 - Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
PY - 2018/12
Y1 - 2018/12
N2 - 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. FUND: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
AB - 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. FUND: European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
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U2 - 10.1016/j.ebiom.2018.10.066
DO - 10.1016/j.ebiom.2018.10.066
M3 - Article
C2 - 30442561
VL - 38
SP - 206
EP - 216
JO - Ebiomedicine
JF - Ebiomedicine
SN - 2352-3964
ER -
