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

Priyanka Parmar; Estelle Lowry; Giovanni Cugliari; Matthew Suderman; Rory Wilson; Ville Karhunen; Toby Andrew; Petri Wiklund; Matthias Wielscher; Simonetta Guarrera; Alexander Teumer; Benjamin Lehne; Lili Milani; Niek de Klein; Pashupati P. Mishra; Phillip E. Melton; Pooja R. Mandaviya; Silva Kasela; Jana Nano; Weihua Zhang; Yan Zhang; Andre G. Uitterlinden; Annette Peters; Ben Schoettker; Christian Gieger; Denise Anderson; Dorret Boomsma; Hans J. Grabe; Salvatore Panico; Jan H. Veldink; Joyce B. J. van Meurs; Leonard van den Berg; Lawrence J. Beilin; Lude Franke; Marie Loh; Marleen M. J. van Greevenbroek; Matthias Nauck; Mika Kahonen; Mikko A. Hurme; Olli T. Raitakari; Oscar H. Franco; P. Eline Slagboom; Pim van der Harst; Sonja Kunze; Stephan B. Felix; Tao Zhang; Wei Chen; Trevor A. Mori; Amelie Bonnefond; Bastiaan T. Heijmans; BIOS Consortium; GLOBAL Meth QTL Consortium; Marjo-Riitta Jarvelin; Sylvain Sebert

doi:10.1016/j.ebiom.2018.10.066

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

Priyanka Parmar, Estelle Lowry, Giovanni Cugliari, Matthew Suderman, Rory Wilson, Ville Karhunen, Toby Andrew, Petri Wiklund, Matthias Wielscher, Simonetta Guarrera, Alexander Teumer, Benjamin Lehne, Lili Milani, Niek de Klein, Pashupati P. Mishra, Phillip E. Melton, Pooja R. Mandaviya, Silva Kasela, Jana Nano, Weihua ZhangYan Zhang, Andre G. Uitterlinden, Annette Peters, Ben Schoettker, Christian Gieger, Denise Anderson, Dorret Boomsma, Hans J. Grabe, Salvatore Panico, Jan H. Veldink, Joyce B. J. van Meurs, Leonard van den Berg, Lawrence J. Beilin, Lude Franke, Marie Loh, Marleen M. J. van Greevenbroek, Matthias Nauck, Mika Kahonen, Mikko A. Hurme, Olli T. Raitakari, Oscar H. Franco, P. Eline Slagboom, Pim van der Harst, Sonja Kunze, Stephan B. Felix, Tao Zhang, Wei Chen, Trevor A. Mori, Amelie Bonnefond, Bastiaan T. Heijmans, BIOS Consortium, GLOBAL Meth QTL Consortium, Marjo-Riitta Jarvelin^*, Sylvain Sebert^*

^*Corresponding author for this work

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 x 10(-7) <P <0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 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. (c) 2018 The Authors. Published by Elsevier B.V.

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

Keywords

EPIGENOME-WIDE ASSOCIATION
DNA METHYLATION
CARDIOVASCULAR-DISEASE
CIGARETTE-SMOKING
BIRTH-WEIGHT
PREGNANCY
CESSATION
EXPOSURE
RISK
DIET

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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. P., Melton, P. E., Mandaviya, P. R., Kasela, S., Nano, J., ... Sebert, S. (2018). Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults. EBioMedicine, 38, 206-216. https://doi.org/10.1016/j.ebiom.2018.10.066

@article{e402eb71454e47e1a41e0e1ffbe7eaa0,

title = "Association of maternal prenatal smoking GFI1-locus and cardiometabolic 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 x 10(-7) <P <0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 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. (c) 2018 The Authors. Published by Elsevier B.V.",

keywords = "EPIGENOME-WIDE ASSOCIATION, DNA METHYLATION, CARDIOVASCULAR-DISEASE, CIGARETTE-SMOKING, BIRTH-WEIGHT, PREGNANCY, CESSATION, EXPOSURE, RISK, DIET",

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 Schoettker and Christian Gieger and Denise Anderson and Dorret Boomsma 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 Kahonen 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 {BIOS Consortium} and {GLOBAL Meth QTL Consortium} and Marjo-Riitta Jarvelin and Sylvain Sebert",

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",

}

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, Schoettker, B, Gieger, C, Anderson, D, Boomsma, D, Grabe, HJ, Panico, S, Veldink, JH, van Meurs, JBJ, van den Berg, L, Beilin, LJ, Franke, L, Loh, M, van Greevenbroek, MMJ, Nauck, M, Kahonen, 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, BIOS Consortium, GLOBAL Meth QTL Consortium, Jarvelin, M-R & Sebert, S 2018, 'Association of maternal prenatal smoking GFI1-locus and cardiometabolic phenotypes in 18,212 adults', EBioMedicine, vol. 38, pp. 206-216. https://doi.org/10.1016/j.ebiom.2018.10.066

TY - JOUR

T1 - Association of maternal prenatal smoking GFI1-locus and cardiometabolic 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 - Schoettker, Ben

AU - Gieger, Christian

AU - Anderson, Denise

AU - Boomsma, Dorret

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 - Kahonen, 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 - BIOS Consortium

AU - GLOBAL Meth QTL Consortium

AU - Jarvelin, Marjo-Riitta

AU - Sebert, Sylvain

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 x 10(-7) <P <0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 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. (c) 2018 The Authors. Published by Elsevier B.V.

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 x 10(-7) <P <0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 x 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. (c) 2018 The Authors. Published by Elsevier B.V.

KW - EPIGENOME-WIDE ASSOCIATION

KW - DNA METHYLATION

KW - CARDIOVASCULAR-DISEASE

KW - CIGARETTE-SMOKING

KW - BIRTH-WEIGHT

KW - PREGNANCY

KW - CESSATION

KW - EXPOSURE

KW - RISK

KW - DIET

U2 - 10.1016/j.ebiom.2018.10.066

DO - 10.1016/j.ebiom.2018.10.066

M3 - Article

SN - 2352-3964

VL - 38

SP - 206

EP - 216

JO - EBioMedicine

JF - EBioMedicine

ER -