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

Dorret I. Boomsma; for the BIOS Consortium; for the GLOBAL Meth QTL Consortium

doi:10.1016/j.ebiom.2018.10.066

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

Dorret I. Boomsma, for the BIOS Consortium, for the GLOBAL Meth QTL Consortium

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	206-216
Number of pages	11
Journal	Ebiomedicine
Volume	38
Early online date	13 Nov 2018
DOIs	https://doi.org/10.1016/j.ebiom.2018.10.066
Publication status	Published - Dec 2018

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10.1016/j.ebiom.2018.10.066

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@article{1715defeb26c4b97b30fd6f2051d52bc,

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

abstract = "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.",

author = "Priyanka Parmar and Estelle Lowry and Giovanni Cugliari and Matthew Suderman and Rory Wilson and Ville Karhunen and Toby Andrew and Petri Wiklund and Matthias Wielscher and Simonetta Guarrera and Alexander Teumer and Benjamin Lehne and Lili Milani and {de Klein}, Niek and Mishra, {Pashupati P.} and Melton, {Phillip E.} and Mandaviya, {Pooja R.} and Silva Kasela and Jana Nano and Weihua Zhang and Yan Zhang and Uitterlinden, {Andre G.} and Annette Peters and Ben Sch{\"o}ttker and Christian Gieger and Denise Anderson and Boomsma, {Dorret I.} and Grabe, {Hans J.} and Salvatore Panico and Veldink, {Jan H.} and {van Meurs}, {Joyce B.J.} and {van den Berg}, Leonard and Beilin, {Lawrence J.} and Lude Franke and Marie Loh and {van Greevenbroek}, {Marleen M.J.} and Matthias Nauck and Mika K{\"a}h{\"o}nen and Hurme, {Mikko A.} and Raitakari, {Olli T.} and Franco, {Oscar H.} and Slagboom, {P. Eline} and {van der Harst}, Pim and Sonja Kunze and Felix, {Stephan B.} and Tao Zhang and Wei Chen and Mori, {Trevor A.} and Amelie Bonnefond and Heijmans, {Bastiaan T.} and Taulant Muka and Kooner, {Jaspal S.} and Krista Fischer and Melanie Waldenberger and Philippe Froguel and Huang, {Rae Chi} and Terho Lehtim{\"a}ki and Wolfgang Rathmann and Relton, {Caroline L.} and Giuseppe Matullo and Hermann Brenner and Niek Verweij and Shengxu Li and Chambers, {John C.} and J{\"a}rvelin, {Marjo Riitta} and Sylvain Sebert and {for the BIOS Consortium} and {for the GLOBAL Meth QTL Consortium}",

year = "2018",

month = dec,

doi = "10.1016/j.ebiom.2018.10.066",

language = "English",

volume = "38",

pages = "206--216",

journal = "Ebiomedicine",

issn = "2352-3964",

publisher = "Elsevier BV",

}

TY - JOUR

T1 - Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults

AU - Parmar, Priyanka

AU - Lowry, Estelle

AU - Cugliari, Giovanni

AU - Suderman, Matthew

AU - Wilson, Rory

AU - Karhunen, Ville

AU - Andrew, Toby

AU - Wiklund, Petri

AU - Wielscher, Matthias

AU - Guarrera, Simonetta

AU - Teumer, Alexander

AU - Lehne, Benjamin

AU - Milani, Lili

AU - de Klein, Niek

AU - Mishra, Pashupati P.

AU - Melton, Phillip E.

AU - Mandaviya, Pooja R.

AU - Kasela, Silva

AU - Nano, Jana

AU - Zhang, Weihua

AU - Zhang, Yan

AU - Uitterlinden, Andre G.

AU - Peters, Annette

AU - Schöttker, Ben

AU - Gieger, Christian

AU - Anderson, Denise

AU - Boomsma, Dorret I.

AU - Grabe, Hans J.

AU - Panico, Salvatore

AU - Veldink, Jan H.

AU - van Meurs, Joyce B.J.

AU - van den Berg, Leonard

AU - Beilin, Lawrence J.

AU - Franke, Lude

AU - Loh, Marie

AU - van Greevenbroek, Marleen M.J.

AU - Nauck, Matthias

AU - Kähönen, Mika

AU - Hurme, Mikko A.

AU - Raitakari, Olli T.

AU - Franco, Oscar H.

AU - Slagboom, P. Eline

AU - van der Harst, Pim

AU - Kunze, Sonja

AU - Felix, Stephan B.

AU - Zhang, Tao

AU - Chen, Wei

AU - Mori, Trevor A.

AU - Bonnefond, Amelie

AU - Heijmans, Bastiaan T.

AU - Muka, Taulant

AU - Kooner, Jaspal S.

AU - Fischer, Krista

AU - Waldenberger, Melanie

AU - Froguel, Philippe

AU - Huang, Rae Chi

AU - Lehtimäki, Terho

AU - Rathmann, Wolfgang

AU - Relton, Caroline L.

AU - Matullo, Giuseppe

AU - Brenner, Hermann

AU - Verweij, Niek

AU - Li, Shengxu

AU - Chambers, John C.

AU - Järvelin, Marjo Riitta

AU - Sebert, Sylvain

AU - for the BIOS Consortium

AU - for the GLOBAL Meth QTL Consortium

PY - 2018/12

Y1 - 2018/12

N2 - 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.

AB - 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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U2 - 10.1016/j.ebiom.2018.10.066

DO - 10.1016/j.ebiom.2018.10.066

M3 - Article

C2 - 30442561

VL - 38

SP - 206

EP - 216

JO - Ebiomedicine

JF - Ebiomedicine

SN - 2352-3964

ER -

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

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