Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults

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. We meta-analysed the...

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Published in:EBioMedicine 2018-12, Vol.38, p.206-216
Main Authors: 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, 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, 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, Mori, Trevor A., Bonnefond, Amelie, Heijmans, Bastiaan T., Muka, Taulant, Kooner, Jaspal S., Fischer, Krista, Waldenberger, Melanie, Froguel, Philippe, Huang, Rae-Chi, Lehtimäki, Terho, Rathmann, Wolfgang, Relton, Caroline L., Matullo, Giuseppe, Brenner, Hermann, Verweij, Niek, Li, Shengxu, Chambers, John C., Järvelin, Marjo-Riitta, Sebert, Sylvain
Format: Article
Language:English
Subjects:
Adult
Biomarkers
CpG Islands
Disease Susceptibility
DNA Methylation
DNA-Binding Proteins - genetics
Energy Metabolism
Epigenesis, Genetic
Female
Genetic Loci
Humans
Life Sciences
Male
Maternal Exposure - adverse effects
Middle Aged
Myocardium - metabolism
Phenotype
Population Surveillance
Pregnancy
Prenatal Exposure Delayed Effects
Research paper
Smoking - adverse effects
Transcription Factors - genetics
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Summary: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. 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). 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 
ISSN:2352-3964
2352-3964
DOI:10.1016/j.ebiom.2018.10.066