EBioMedicine (Dec 2018)
Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adultsResearch in context
- 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 Schöttker,
- Christian Gieger,
- Denise Anderson,
- Dorret I. 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 Kähönen,
- 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,
- Taulant Muka,
- Jaspal S. Kooner,
- Krista Fischer,
- Melanie Waldenberger,
- Philippe Froguel,
- Rae-Chi Huang,
- Terho Lehtimäki,
- Wolfgang Rathmann,
- Caroline L. Relton,
- Giuseppe Matullo,
- Hermann Brenner,
- Niek Verweij,
- Shengxu Li,
- John C. Chambers,
- Marjo-Riitta Järvelin,
- Sylvain Sebert
Affiliations
- Priyanka Parmar
- Center for Life Course Health Research, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland
- Estelle Lowry
- Center for Life Course Health Research, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland
- Giovanni Cugliari
- Department of Medical Sciences, University of Turin, Turin, Italy; Italian Institute for Genomic Medicine, IIGM, Turin, Italy
- Matthew Suderman
- MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, UK
- Rory Wilson
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Bavaria, Germany; Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Bavaria, Germany
- Ville Karhunen
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London
- Toby Andrew
- Genomics of Common Disease, Department of Medicine, Imperial College London, London, UK
- Petri Wiklund
- Center for Life Course Health Research, University of Oulu, Oulu, Finland; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London; Department of Health Sciences, University of Jyväskylä, Jyväskylä, Finland
- Matthias Wielscher
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London
- Simonetta Guarrera
- Department of Medical Sciences, University of Turin, Turin, Italy; Italian Institute for Genomic Medicine, IIGM, Turin, Italy
- Alexander Teumer
- Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany; Partner Site Greifswald, DZHK (German Centre for Cardiovascular Research), Greifswald, Germany
- Benjamin Lehne
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London
- Lili Milani
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia; Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden
- Niek de Klein
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
- Pashupati P. Mishra
- Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Centre - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Phillip E. Melton
- School of Pharmacy and Biomedical Sciences, Curtin University, Bentley, Australia; Curtin UWA Centre for Genetic Origins of Health and Disease, School of Biomedical Sciences, The University of Western Australia, Crawley, Australia
- Pooja R. Mandaviya
- Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Silva Kasela
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
- Jana Nano
- Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Bavaria, Germany; Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Weihua Zhang
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London; Department of Cardiology, Ealing Hospital, North West Healthcare NHS Trust, London, UK
- Yan Zhang
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany
- Andre G. Uitterlinden
- Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands; Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Annette Peters
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Bavaria, Germany; Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Bavaria, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
- Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany; Network Aging Research, University of Heidelberg, Bergheimer Straße, Heidelberg, Germany
- Christian Gieger
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Bavaria, Germany; Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Bavaria, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
- Denise Anderson
- Telethon Kids Institute, University of Western Australia, Perth, Australia
- Dorret I. Boomsma
- Department of Biological Psychology, School of Public Health, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands
- Hans J. Grabe
- Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany; German Centre for Neurodegenerative Diseases DZNE, Site Rostock/Greifswald, Greifswald, Germany
- Salvatore Panico
- Department of Clinical Medicine and Surgery, Federico II University, Naples, Italy
- Jan H. Veldink
- Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands
- Joyce B.J. van Meurs
- Department of Internal Medicine, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Leonard van den Berg
- Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, The Netherlands
- Lawrence J. Beilin
- Medical School, University of Western Australia, Perth, Australia
- Lude Franke
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
- Marie Loh
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London; Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Level 5, Singapore, Singapore; Institute of Health Sciences, University of Oulu, Finland
- Marleen M.J. van Greevenbroek
- Department of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Centre, Maastricht, The Netherlands
- Matthias Nauck
- Partner Site Greifswald, DZHK (German Centre for Cardiovascular Research), Greifswald, Germany; Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany
- Mika Kähönen
- Department of Clinical Physiology, Tampere University Hospital, Tampere, Finland; Department of Clinical Physiology, Finnish Cardiovascular Research Centre - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Mikko A. Hurme
- Department of Microbiology and Immunology, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Olli T. Raitakari
- Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku, Finland; Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
- Oscar H. Franco
- Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- P.Eline Slagboom
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands
- Pim van der Harst
- Department of Genetics, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands; Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands; Durrer Centre for Cardiogenetic Research, ICIN - Netherlands Heart Institute, Utrecht, The Netherlands
- Sonja Kunze
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Bavaria, Germany; Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Bavaria, Germany
- Stephan B. Felix
- Partner Site Greifswald, DZHK (German Centre for Cardiovascular Research), Greifswald, Germany
- Tao Zhang
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, USA; Department of Biostatistics, School of Public Health, Shandong University, Jinan, China
- Wei Chen
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, USA
- Trevor A. Mori
- Medical School, University of Western Australia, Perth, Australia
- Amelie Bonnefond
- Genomics of Common Disease, Department of Medicine, Imperial College London, London, UK; European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, CNRS UMR 8199, Lille, France
- Bastiaan T. Heijmans
- Molecular Epidemiology, Department of Biomedical Data Sciences, Leiden University Medical Centre, Leiden, The Netherlands
- Taulant Muka
- Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, The Netherlands
- Jaspal S. Kooner
- Department of Cardiology, Ealing Hospital, North West Healthcare NHS Trust, London, UK; Imperial College Healthcare NHS Trust, London, UK; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London; Imperial College London, National Heart and Lung Institute, London, UK
- Krista Fischer
- Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
- Melanie Waldenberger
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Centre for Environmental Health, Neuherberg, Bavaria, Germany; Helmholtz Zentrum München, German Research Centre for Environmental Health, Institute of Epidemiology, Neuherberg, Bavaria, Germany; German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
- Philippe Froguel
- Genomics of Common Disease, Department of Medicine, Imperial College London, London, UK; European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, CNRS UMR 8199, Lille, France
- Rae-Chi Huang
- Telethon Kids Institute, University of Western Australia, Perth, Australia
- Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland; Department of Clinical Chemistry, Finnish Cardiovascular Research Centre - Tampere, Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland
- Wolfgang Rathmann
- Institute for Biometrics and Epidemiology, German Diabetes Centre, Leibniz Centre for Diabetes Research at Heinrich, Heine University, Düsseldorf, Germany
- Caroline L. Relton
- MRC Integrative Epidemiology Unit, Population Health Sciences, Bristol Medical School, University of Bristol, UK
- Giuseppe Matullo
- Department of Medical Sciences, University of Turin, Turin, Italy; Italian Institute for Genomic Medicine, IIGM, Turin, Italy
- Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Centre (DKFZ), Im Neuenheimer Feld, Heidelberg, Germany; Network Aging Research, University of Heidelberg, Bergheimer Straße, Heidelberg, Germany
- Niek Verweij
- Department of Cardiology, University Medical Centre Groningen, University of Groningen, Groningen, The Netherlands
- Shengxu Li
- Children's Hospitals and Clinics of Minnesota, Children's Minnesota Research Institute, Minneapolis, MN 55404, USA
- John C. Chambers
- Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London; Department of Cardiology, Ealing Hospital, North West Healthcare NHS Trust, London, UK; Imperial College Healthcare NHS Trust, London, UK; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore
- Marjo-Riitta Järvelin
- Center for Life Course Health Research, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London, London; Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK; Correspondence to: Marjo-Riitta Järvelin, Department of Epidemiology and Biostatistics, Faculty of Medicine, Imperial College London, St. Mary's campus, UK.
- Sylvain Sebert
- Center for Life Course Health Research, University of Oulu, Oulu, Finland; Biocenter Oulu, University of Oulu, Oulu, Finland; Medical Research Centre (MRC) Oulu, Oulu University Hospital, University of Oulu, Oulu, Finland; Correspondence to: Sylvain Sebert, Centre for Life Course Health Research, Faculty of Medicine, University of Oulu, P.O. Box 5000, Oulu 90014, Finland.
- Journal volume & issue
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Vol. 38
pp. 206 – 216
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.
