Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes

• Pooja R. Mandaviya ,

  Contributed equally to this work with: Pooja R. Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E. Marioni, Vinh Truong

  Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Visualization, Writing – original draft, Writing – review & editing

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands, Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

  http://orcid.org/0000-0002-7730-4462

  ⨯
• Roby Joehanes ,

  Contributed equally to this work with: Pooja R. Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E. Marioni, Vinh Truong

  Roles Formal analysis, Investigation, Resources, Software, Writing – review & editing

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliation Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, MA, United States of America

  ⨯
• Dylan Aïssi ,

  Contributed equally to this work with: Pooja R. Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E. Marioni, Vinh Truong

  Roles Formal analysis, Investigation, Methodology, Writing – review & editing

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France, ICAN Institute for Cardiometabolism and Nutrition, Paris, France

  ⨯
• Brigitte Kühnel ,

  Contributed equally to this work with: Pooja R. Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E. Marioni, Vinh Truong

  Roles Formal analysis, Investigation

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

  ⨯
• Riccardo E. Marioni ,

  Contributed equally to this work with: Pooja R. Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E. Marioni, Vinh Truong

  Roles Formal analysis, Investigation, Methodology

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Queensland Brain Institute, The University of Queensland, Brisbane, Australia, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom, Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom

  ⨯
• Vinh Truong ,

  Contributed equally to this work with: Pooja R. Mandaviya, Roby Joehanes, Dylan Aïssi, Brigitte Kühnel, Riccardo E. Marioni, Vinh Truong

  Roles Formal analysis, Investigation

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliation Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

  ⨯
• Lisette Stolk,

  Roles Conceptualization, Data curation, Investigation, Methodology, Supervision

  Affiliation Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

  ⨯
• Marian Beekman,

  Roles Project administration, Writing – review & editing

  Affiliation Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands

  ⨯
• Marc Jan Bonder,

  Roles Investigation, Resources

  Affiliation Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands

  ⨯
• Lude Franke,

  Roles Investigation, Resources

  Affiliation Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands

  ⨯
• Christian Gieger,

  Roles Writing – review & editing

  Affiliations Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

  ⨯
• Tianxiao Huan,

  Roles Data curation, Writing – review & editing

  Affiliations Framingham Heart Study, Framingham, MA, United States of America, The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America

  ⨯
• M. Arfan Ikram,

  Roles Investigation, Writing – review & editing

  Affiliation Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands

  ⨯
• Sonja Kunze,

  Roles Investigation, Writing – review & editing

  Affiliations Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

  ⨯
• Liming Liang,

  Roles Data curation

  Affiliation Harvard T.H. Chan School of Public Health, Boston, MA, United States of America

  ⨯
• Jan Lindemans,

  Roles Conceptualization, Methodology, Project administration, Resources, Supervision, Writing – review & editing

  Affiliation Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands

  ⨯
• Chunyu Liu,

  Roles Data curation, Writing – review & editing

  Affiliations Framingham Heart Study, Framingham, MA, United States of America, The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America

  ⨯
• Allan F. McRae,

  Roles Investigation

  Affiliation Queensland Brain Institute, The University of Queensland, Brisbane, Australia

  ⨯
• Michael M. Mendelson,

  Roles Data curation

  Affiliations Framingham Heart Study, Framingham, MA, United States of America, The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America, Department of Cardiology, Boston Children's Hospital, Boston, MA, United States of America

  ⨯
• Martina Müller-Nurasyid,

  Roles Data curation, Investigation

  Affiliations DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany, Institute of Genetic Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, Department of Medicine I, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Germany

  ⨯
• Annette Peters,

  Roles Investigation, Writing – review & editing

  Affiliations Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany

  ⨯
• P. Eline Slagboom,

  Roles Investigation

  Affiliation Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands

  ⨯
• John M. Starr,

  Roles Investigation

  Affiliation Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom

  ⨯
• David-Alexandre Trégouët,

  Roles Investigation, Writing – review & editing

  Affiliations Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France, ICAN Institute for Cardiometabolism and Nutrition, Paris, France

  ⨯
• André G. Uitterlinden,

  Roles Conceptualization, Investigation, Project administration, Resources, Supervision

  Affiliation Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

  ⨯
• Marleen M. J. van Greevenbroek,

  Roles Investigation, Project administration, Resources, Writing – review & editing

  Affiliation Department of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands

  ⨯
• Diana van Heemst,

  Roles Writing – review & editing

  Affiliation Department of Gerontology and Geriatrics Section, Leiden University Medical Center, Leiden, The Netherlands

  ⨯
• Maarten van Iterson,

  Roles Data curation, Resources, Software

  Affiliation Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands

  ⨯
• Philip S. Wells,

  Roles Investigation, Project administration

  Affiliation Department of Medicine, University of Ottawa, and the Ottawa Hospital Research Institute, Ottawa, Canada

  ⨯
• Chen Yao,

  Roles Data curation

  Affiliations Framingham Heart Study, Framingham, MA, United States of America, The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America

  ⨯
• Ian J. Deary ,

  Roles Investigation

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom, Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom

  ⨯
• France Gagnon ,

  Roles Investigation, Supervision, Writing – review & editing

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliation Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada

  ⨯
• Bastiaan T. Heijmans ,

  Roles Investigation, Project administration, Resources, Supervision, Writing – review & editing

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliation Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands

  ⨯
• Daniel Levy ,

  Roles Investigation, Writing – review & editing

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Framingham Heart Study, Framingham, MA, United States of America, The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America

  ⨯
• Pierre-Emmanuel Morange ,

  Roles Investigation

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Laboratory of Haematology, La Timone Hospital, Marseille, France, Institut National pour la Santé et la Recherche Médicale (INSERM), UMR_S 1062, Inra UMR_1260, Aix-Marseille Université, Marseille, France

  ⨯
• Melanie Waldenberger ,

  Roles Investigation

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliations Research Unit of Molecular Epidemiology, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany, Institute of Epidemiology II, Helmholtz Zentrum München—German Research Center for Environmental Health, Neuherberg, Germany

  ⨯
• Sandra G. Heil ,

  Roles Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliation Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands

  ⨯
• Joyce B. J. van Meurs ,

  Roles Conceptualization, Investigation, Methodology, Project administration, Resources, Supervision, Writing – review & editing

  * E-mail: j.vanmeurs@erasmusmc.nl

  ¶‡ PRM, RJ, DA, BK, REM, and VT are first authors on this work. IJD, FG, BTH, DL, PEM, MW, SGH, and JBJvM also contributed equally as last authors on this work.

  Affiliation Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands

  ⨯
•  [ ... ],
• on behalf of The CHARGE Consortium Epigenetics group and BIOS Consortium

  ¶Membership of the CHARGE Consortium Epigenetics group and BIOS Consortium is provided in the S1 and S2 Files, respectively.

  ⨯
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