Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults
MetadataShow full item record
Please see the attached document for a complete list of authors
© 2018 The Authors 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.
Showing items related by title, author, creator and subject.
Zhang, Y.; Florath, Ines; Saum, K.; Brenner, H. (2016)BACKGROUND: Epigenome-wide profiling of DNA methylation pattern with respect to tobacco smoking has given rise to a new measure of smoking exposure. We investigated the relationships of methylation markers with both ...
Giglia, Roslyn Carmel (2007)The consumption of alcohol and smoking of cigarettes are both common practices in Australian society. With continued public health efforts exposure to both alcohol and nicotine during pregnancy has diminished, however ...
Replacing sitting time with standing or stepping: associations with cardio-metabolic risk biomarkersHealy, Genevieve; Winkler, E.; Owen, N.; Anuradha, S.; Dunstan, D. (2015)Aims: While excessive sitting time is related adversely to cardio-metabolic health, it is unknown whether standing is a suitable replacement activity or whether ambulatory movement is required. Using isotemporal substitution ...