A1 Refereed original research article in a scientific journal
Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults
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 P., Melton P., Mandaviya P., Kasela S., Nano J., Zhang W., Zhang Y., Uitterlinden A., Peters A., Schöttker B., Gieger C., Anderson D., Boomsma D., Grabe H., Panico S., Veldink J., van Meurs J., van den Berg L., Beilin L., Franke L., Loh M., van Greevenbroek M., Nauck M., Kähönen M., Hurme M., Raitakari O., Franco O., Slagboom P., van der Harst P., Kunze S., Felix S., Zhang T., Chen W., Mori T., Bonnefond A., Heijmans B., Muka T., Kooner J., Fischer K., Waldenberger M., Froguel P., Huang R., Lehtimäki T., Rathmann W., Relton C., Matullo G., Brenner H., Verweij N., Li S., Chambers J., Järvelin M., Sebert S., Järvelin M., Sebert S., Li S., Chambers J., Brenner H., Verweij N.
Publisher: Elsevier B.V.
Publication year: 2018
Journal: EBioMedicine
Journal name in source: EBioMedicine
Volume: 38
First page : 206
Last page: 216
Number of pages: 11
ISSN: 2352-3964
eISSN: 2352-3964
DOI: https://doi.org/10.1016/j.ebiom.2018.10.066
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/37223047
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.
Downloadable publication This is an electronic reprint of the original article. |  |
