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.

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Overview publication

Title	Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults.
Date	December 1st, 2018
Issue name	EBioMedicine
Issue number	v38:206-216
DOI	10.1016/j.ebiom.2018.10.066
Authors	Parmar P, Lowry E, Cugliari G, Suderman M, Wilson R, Karhunen V, Andrew T, Wiklund P, Wielscher M, Guarrera S, Teumer A, Lehne B, Milani L, de Klein N, Mishra PP, Melton PE, Mandaviya PR, Kasela S, Nano J, Zhang W, Zhang Y, Uitterlinden AG, Peters A, Schöttker B, Gieger C, Anderson D, Boomsma DI, Grabe HJ, Panico S, Veldink JH, van Meurs JBJ, van den Berg L, Beilin LJ, Franke L, Loh M, van Greevenbroek MMJ, Nauck M, Kähönen M, Hurme MA, Raitakari OT, Franco OH, Slagboom PE, van der Harst P, Kunze S, Felix SB, Zhang T, Chen W, Mori TA, Bonnefond A, Heijmans BT, Muka T, Kooner JS, Fischer K, Waldenberger M, Froguel P, Huang RC, Lehtimäki T, Rathmann W, Relton CL, Matullo G, Brenner H, Verweij N, Li S, Chambers JC, Järvelin MR & Sebert S
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