Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults
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.
|This work was funded by the European Commission 7th Framework Programme; grant id h2020/692145 - Rise of scientific excellence and collaboration for implementing personalised medicine in Estonia (ePerMed), This work was funded by the European Commission 7th Framework Programme; grant id h2020/643774 - Family-based intervention to improve healthy lifestyle and prevent Type 2 Diabetes amongst South Asians with central obesity and prediabetes (iHealth-T2D), This work was funded by the European Commission 7th Framework Programme; grant id h2020/733206 - Early-life stressors and LifeCycle health (LIFECYCLE), This work was funded by the European Commission 7th Framework Programme; grant id h2020/633595 - Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging (DYNAHEALTH), This work was funded by the European Commission 7th Framework Programme; grant id fp7/279143 - Identification of epigenetic markers underlying increased risk of T2D in South Asians (EPI-MIGRANT)|
|Organisation||Department of Internal Medicine|
Parmar, P. (Priyanka), Lowry, E. (Estelle), Cugliari, G. (Giovanni), Suderman, M.J, Wilson, R, Karhunen, V. (Ville), … Sebert, S. (Sylvain). (2018). Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults. EBioMedicine. doi:10.1016/j.ebiom.2018.10.066