Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.
Identifieur interne : 000339 ( PubMed/Corpus ); précédent : 000338; suivant : 000340Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.
Auteurs : Pooja R. Mandaviya ; Roby Joehanes ; Dylan Aïssi ; Brigitte Kühnel ; Riccardo E. Marioni ; Vinh Truong ; Lisette Stolk ; Marian Beekman ; Marc Jan Bonder ; Lude Franke ; Christian Gieger ; Tianxiao Huan ; M Arfan Ikram ; Sonja Kunze ; Liming Liang ; Jan Lindemans ; Chunyu Liu ; Allan F. Mcrae ; Michael M. Mendelson ; Martina Müller-Nurasyid ; Annette Peters ; P Eline Slagboom ; John M. Starr ; David-Alexandre Trégouët ; André G. Uitterlinden ; Marleen M J. Van Greevenbroek ; Diana Van Heemst ; Maarten Van Iterson ; Philip S. Wells ; Chen Yao ; Ian J. Deary ; France Gagnon ; Bastiaan T. Heijmans ; Daniel Levy ; Pierre-Emmanuel Morange ; Melanie Waldenberger ; Sandra G. Heil ; Joyce B J. Van MeursSource :
- PloS one [ 1932-6203 ] ; 2017.
Abstract
DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation.
DOI: 10.1371/journal.pone.0182472
PubMed: 29084233
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.</title><author><name sortKey="Mandaviya, Pooja R" sort="Mandaviya, Pooja R" uniqKey="Mandaviya P" first="Pooja R" last="Mandaviya">Pooja R. Mandaviya</name><affiliation><nlm:affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Joehanes, Roby" sort="Joehanes, Roby" uniqKey="Joehanes R" first="Roby" last="Joehanes">Roby Joehanes</name><affiliation><nlm:affiliation>Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Aissi, Dylan" sort="Aissi, Dylan" uniqKey="Aissi D" first="Dylan" last="Aïssi">Dylan Aïssi</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kuhnel, Brigitte" sort="Kuhnel, Brigitte" uniqKey="Kuhnel B" first="Brigitte" last="Kühnel">Brigitte Kühnel</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Marioni, Riccardo E" sort="Marioni, Riccardo E" uniqKey="Marioni R" first="Riccardo E" last="Marioni">Riccardo E. Marioni</name><affiliation><nlm:affiliation>Queensland Brain Institute, The University of Queensland, Brisbane, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Truong, Vinh" sort="Truong, Vinh" uniqKey="Truong V" first="Vinh" last="Truong">Vinh Truong</name><affiliation><nlm:affiliation>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Stolk, Lisette" sort="Stolk, Lisette" uniqKey="Stolk L" first="Lisette" last="Stolk">Lisette Stolk</name><affiliation><nlm:affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Beekman, Marian" sort="Beekman, Marian" uniqKey="Beekman M" first="Marian" last="Beekman">Marian Beekman</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Bonder, Marc Jan" sort="Bonder, Marc Jan" uniqKey="Bonder M" first="Marc Jan" last="Bonder">Marc Jan Bonder</name><affiliation><nlm:affiliation>Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Franke, Lude" sort="Franke, Lude" uniqKey="Franke L" first="Lude" last="Franke">Lude Franke</name><affiliation><nlm:affiliation>Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Huan, Tianxiao" sort="Huan, Tianxiao" uniqKey="Huan T" first="Tianxiao" last="Huan">Tianxiao Huan</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name><affiliation><nlm:affiliation>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Kunze, Sonja" sort="Kunze, Sonja" uniqKey="Kunze S" first="Sonja" last="Kunze">Sonja Kunze</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Liang, Liming" sort="Liang, Liming" uniqKey="Liang L" first="Liming" last="Liang">Liming Liang</name><affiliation><nlm:affiliation>Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Lindemans, Jan" sort="Lindemans, Jan" uniqKey="Lindemans J" first="Jan" last="Lindemans">Jan Lindemans</name><affiliation><nlm:affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Chunyu" sort="Liu, Chunyu" uniqKey="Liu C" first="Chunyu" last="Liu">Chunyu Liu</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Mcrae, Allan F" sort="Mcrae, Allan F" uniqKey="Mcrae A" first="Allan F" last="Mcrae">Allan F. Mcrae</name><affiliation><nlm:affiliation>Queensland Brain Institute, The University of Queensland, Brisbane, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Mendelson, Michael M" sort="Mendelson, Michael M" uniqKey="Mendelson M" first="Michael M" last="Mendelson">Michael M. Mendelson</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name><affiliation><nlm:affiliation>DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P Eline" last="Slagboom">P Eline Slagboom</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Greevenbroek, Marleen M J" sort="Van Greevenbroek, Marleen M J" uniqKey="Van Greevenbroek M" first="Marleen M J" last="Van Greevenbroek">Marleen M J. Van Greevenbroek</name><affiliation><nlm:affiliation>Department of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Heemst, Diana" sort="Van Heemst, Diana" uniqKey="Van Heemst D" first="Diana" last="Van Heemst">Diana Van Heemst</name><affiliation><nlm:affiliation>Department of Gerontology and Geriatrics Section, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Iterson, Maarten" sort="Van Iterson, Maarten" uniqKey="Van Iterson M" first="Maarten" last="Van Iterson">Maarten Van Iterson</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Wells, Philip S" sort="Wells, Philip S" uniqKey="Wells P" first="Philip S" last="Wells">Philip S. Wells</name><affiliation><nlm:affiliation>Department of Medicine, University of Ottawa, and the Ottawa Hospital Research Institute, Ottawa, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Yao, Chen" sort="Yao, Chen" uniqKey="Yao C" first="Chen" last="Yao">Chen Yao</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Gagnon, France" sort="Gagnon, France" uniqKey="Gagnon F" first="France" last="Gagnon">France Gagnon</name><affiliation><nlm:affiliation>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Heijmans, Bastiaan T" sort="Heijmans, Bastiaan T" uniqKey="Heijmans B" first="Bastiaan T" last="Heijmans">Bastiaan T. Heijmans</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Morange, Pierre Emmanuel" sort="Morange, Pierre Emmanuel" uniqKey="Morange P" first="Pierre-Emmanuel" last="Morange">Pierre-Emmanuel Morange</name><affiliation><nlm:affiliation>Laboratory of Haematology, La Timone Hospital, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Waldenberger, Melanie" sort="Waldenberger, Melanie" uniqKey="Waldenberger M" first="Melanie" last="Waldenberger">Melanie Waldenberger</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Heil, Sandra G" sort="Heil, Sandra G" uniqKey="Heil S" first="Sandra G" last="Heil">Sandra G. Heil</name><affiliation><nlm:affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Meurs, Joyce B J" sort="Van Meurs, Joyce B J" uniqKey="Van Meurs J" first="Joyce B J" last="Van Meurs">Joyce B J. Van Meurs</name><affiliation><nlm:affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2017">2017</date><idno type="RBID">pubmed:29084233</idno><idno type="pmid">29084233</idno><idno type="doi">10.1371/journal.pone.0182472</idno><idno type="wicri:Area/PubMed/Corpus">000339</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000339</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.</title><author><name sortKey="Mandaviya, Pooja R" sort="Mandaviya, Pooja R" uniqKey="Mandaviya P" first="Pooja R" last="Mandaviya">Pooja R. Mandaviya</name><affiliation><nlm:affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Joehanes, Roby" sort="Joehanes, Roby" uniqKey="Joehanes R" first="Roby" last="Joehanes">Roby Joehanes</name><affiliation><nlm:affiliation>Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Aissi, Dylan" sort="Aissi, Dylan" uniqKey="Aissi D" first="Dylan" last="Aïssi">Dylan Aïssi</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Kuhnel, Brigitte" sort="Kuhnel, Brigitte" uniqKey="Kuhnel B" first="Brigitte" last="Kühnel">Brigitte Kühnel</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Marioni, Riccardo E" sort="Marioni, Riccardo E" uniqKey="Marioni R" first="Riccardo E" last="Marioni">Riccardo E. Marioni</name><affiliation><nlm:affiliation>Queensland Brain Institute, The University of Queensland, Brisbane, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Truong, Vinh" sort="Truong, Vinh" uniqKey="Truong V" first="Vinh" last="Truong">Vinh Truong</name><affiliation><nlm:affiliation>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Stolk, Lisette" sort="Stolk, Lisette" uniqKey="Stolk L" first="Lisette" last="Stolk">Lisette Stolk</name><affiliation><nlm:affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Beekman, Marian" sort="Beekman, Marian" uniqKey="Beekman M" first="Marian" last="Beekman">Marian Beekman</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Bonder, Marc Jan" sort="Bonder, Marc Jan" uniqKey="Bonder M" first="Marc Jan" last="Bonder">Marc Jan Bonder</name><affiliation><nlm:affiliation>Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Franke, Lude" sort="Franke, Lude" uniqKey="Franke L" first="Lude" last="Franke">Lude Franke</name><affiliation><nlm:affiliation>Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Gieger, Christian" sort="Gieger, Christian" uniqKey="Gieger C" first="Christian" last="Gieger">Christian Gieger</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Huan, Tianxiao" sort="Huan, Tianxiao" uniqKey="Huan T" first="Tianxiao" last="Huan">Tianxiao Huan</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name><affiliation><nlm:affiliation>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Kunze, Sonja" sort="Kunze, Sonja" uniqKey="Kunze S" first="Sonja" last="Kunze">Sonja Kunze</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Liang, Liming" sort="Liang, Liming" uniqKey="Liang L" first="Liming" last="Liang">Liming Liang</name><affiliation><nlm:affiliation>Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Lindemans, Jan" sort="Lindemans, Jan" uniqKey="Lindemans J" first="Jan" last="Lindemans">Jan Lindemans</name><affiliation><nlm:affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Liu, Chunyu" sort="Liu, Chunyu" uniqKey="Liu C" first="Chunyu" last="Liu">Chunyu Liu</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Mcrae, Allan F" sort="Mcrae, Allan F" uniqKey="Mcrae A" first="Allan F" last="Mcrae">Allan F. Mcrae</name><affiliation><nlm:affiliation>Queensland Brain Institute, The University of Queensland, Brisbane, Australia.</nlm:affiliation></affiliation></author><author><name sortKey="Mendelson, Michael M" sort="Mendelson, Michael M" uniqKey="Mendelson M" first="Michael M" last="Mendelson">Michael M. Mendelson</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Muller Nurasyid, Martina" sort="Muller Nurasyid, Martina" uniqKey="Muller Nurasyid M" first="Martina" last="Müller-Nurasyid">Martina Müller-Nurasyid</name><affiliation><nlm:affiliation>DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Peters, Annette" sort="Peters, Annette" uniqKey="Peters A" first="Annette" last="Peters">Annette Peters</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Slagboom, P Eline" sort="Slagboom, P Eline" uniqKey="Slagboom P" first="P Eline" last="Slagboom">P Eline Slagboom</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Starr, John M" sort="Starr, John M" uniqKey="Starr J" first="John M" last="Starr">John M. Starr</name><affiliation><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Tregouet, David Alexandre" sort="Tregouet, David Alexandre" uniqKey="Tregouet D" first="David-Alexandre" last="Trégouët">David-Alexandre Trégouët</name><affiliation><nlm:affiliation>Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.</nlm:affiliation></affiliation></author><author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="André G" last="Uitterlinden">André G. Uitterlinden</name><affiliation><nlm:affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Greevenbroek, Marleen M J" sort="Van Greevenbroek, Marleen M J" uniqKey="Van Greevenbroek M" first="Marleen M J" last="Van Greevenbroek">Marleen M J. Van Greevenbroek</name><affiliation><nlm:affiliation>Department of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Heemst, Diana" sort="Van Heemst, Diana" uniqKey="Van Heemst D" first="Diana" last="Van Heemst">Diana Van Heemst</name><affiliation><nlm:affiliation>Department of Gerontology and Geriatrics Section, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Iterson, Maarten" sort="Van Iterson, Maarten" uniqKey="Van Iterson M" first="Maarten" last="Van Iterson">Maarten Van Iterson</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Wells, Philip S" sort="Wells, Philip S" uniqKey="Wells P" first="Philip S" last="Wells">Philip S. Wells</name><affiliation><nlm:affiliation>Department of Medicine, University of Ottawa, and the Ottawa Hospital Research Institute, Ottawa, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Yao, Chen" sort="Yao, Chen" uniqKey="Yao C" first="Chen" last="Yao">Chen Yao</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Deary, Ian J" sort="Deary, Ian J" uniqKey="Deary I" first="Ian J" last="Deary">Ian J. Deary</name><affiliation><nlm:affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.</nlm:affiliation></affiliation></author><author><name sortKey="Gagnon, France" sort="Gagnon, France" uniqKey="Gagnon F" first="France" last="Gagnon">France Gagnon</name><affiliation><nlm:affiliation>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.</nlm:affiliation></affiliation></author><author><name sortKey="Heijmans, Bastiaan T" sort="Heijmans, Bastiaan T" uniqKey="Heijmans B" first="Bastiaan T" last="Heijmans">Bastiaan T. Heijmans</name><affiliation><nlm:affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Levy, Daniel" sort="Levy, Daniel" uniqKey="Levy D" first="Daniel" last="Levy">Daniel Levy</name><affiliation><nlm:affiliation>Framingham Heart Study, Framingham, MA, United States of America.</nlm:affiliation></affiliation></author><author><name sortKey="Morange, Pierre Emmanuel" sort="Morange, Pierre Emmanuel" uniqKey="Morange P" first="Pierre-Emmanuel" last="Morange">Pierre-Emmanuel Morange</name><affiliation><nlm:affiliation>Laboratory of Haematology, La Timone Hospital, Marseille, France.</nlm:affiliation></affiliation></author><author><name sortKey="Waldenberger, Melanie" sort="Waldenberger, Melanie" uniqKey="Waldenberger M" first="Melanie" last="Waldenberger">Melanie Waldenberger</name><affiliation><nlm:affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</nlm:affiliation></affiliation></author><author><name sortKey="Heil, Sandra G" sort="Heil, Sandra G" uniqKey="Heil S" first="Sandra G" last="Heil">Sandra G. Heil</name><affiliation><nlm:affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author><author><name sortKey="Van Meurs, Joyce B J" sort="Van Meurs, Joyce B J" uniqKey="Van Meurs J" first="Joyce B J" last="Van Meurs">Joyce B J. Van Meurs</name><affiliation><nlm:affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</nlm:affiliation></affiliation></author></analytic><series><title level="j">PloS one</title><idno type="eISSN">1932-6203</idno><imprint><date when="2017" type="published">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation.</div></front></TEI><pubmed><MedlineCitation Status="In-Process" Owner="NLM"><PMID Version="1">29084233</PMID><DateCreated><Year>2017</Year><Month>10</Month><Day>30</Day></DateCreated><DateRevised><Year>2017</Year><Month>11</Month><Day>10</Day></DateRevised><Article PubModel="Electronic-eCollection"><Journal><ISSN IssnType="Electronic">1932-6203</ISSN><JournalIssue CitedMedium="Internet"><Volume>12</Volume><Issue>10</Issue><PubDate><Year>2017</Year></PubDate></JournalIssue><Title>PloS one</Title><ISOAbbreviation>PLoS ONE</ISOAbbreviation></Journal><ArticleTitle>Genetically defined elevated homocysteine levels do not result in widespread changes of DNA methylation in leukocytes.</ArticleTitle><Pagination><MedlinePgn>e0182472</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1371/journal.pone.0182472</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">DNA methylation is affected by the activities of the key enzymes and intermediate metabolites of the one-carbon pathway, one of which involves homocysteine. We investigated the effect of the well-known genetic variant associated with mildly elevated homocysteine: MTHFR 677C>T independently and in combination with other homocysteine-associated variants, on genome-wide leukocyte DNA-methylation.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Methylation levels were assessed using Illumina 450k arrays on 9,894 individuals of European ancestry from 12 cohort studies. Linear-mixed-models were used to study the association of additive MTHFR 677C>T and genetic-risk score (GRS) based on 18 homocysteine-associated SNPs, with genome-wide methylation.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Meta-analysis revealed that the MTHFR 677C>T variant was associated with 35 CpG sites in cis, and the GRS showed association with 113 CpG sites near the homocysteine-associated variants. Genome-wide analysis revealed that the MTHFR 677C>T variant was associated with 1 trans-CpG (nearest gene ZNF184), while the GRS model showed association with 5 significant trans-CpGs annotated to nearest genes PTF1A, MRPL55, CTDSP2, CRYM and FKBP5.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Our results do not show widespread changes in DNA-methylation across the genome, and therefore do not support the hypothesis that mildly elevated homocysteine is associated with widespread methylation changes in leukocytes.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Mandaviya</LastName><ForeName>Pooja R</ForeName><Initials>PR</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-7730-4462</Identifier><AffiliationInfo><Affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Joehanes</LastName><ForeName>Roby</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Institute for Aging Research, Hebrew SeniorLife, Harvard Medical School, Boston, MA, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Aïssi</LastName><ForeName>Dylan</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICAN Institute for Cardiometabolism and Nutrition, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kühnel</LastName><ForeName>Brigitte</ForeName><Initials>B</Initials><AffiliationInfo><Affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Marioni</LastName><ForeName>Riccardo E</ForeName><Initials>RE</Initials><AffiliationInfo><Affiliation>Queensland Brain Institute, The University of Queensland, Brisbane, Australia.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Medical Genetics Section, Centre for Genomic and Experimental Medicine, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Truong</LastName><ForeName>Vinh</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stolk</LastName><ForeName>Lisette</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beekman</LastName><ForeName>Marian</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bonder</LastName><ForeName>Marc Jan</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Franke</LastName><ForeName>Lude</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Department of Genetics, University Medical Center Groningen, Groningen, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gieger</LastName><ForeName>Christian</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Huan</LastName><ForeName>Tianxiao</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Framingham Heart Study, Framingham, MA, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ikram</LastName><ForeName>M Arfan</ForeName><Initials>MA</Initials><AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kunze</LastName><ForeName>Sonja</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liang</LastName><ForeName>Liming</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Harvard T.H. Chan School of Public Health, Boston, MA, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lindemans</LastName><ForeName>Jan</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Chunyu</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Framingham Heart Study, Framingham, MA, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McRae</LastName><ForeName>Allan F</ForeName><Initials>AF</Initials><AffiliationInfo><Affiliation>Queensland Brain Institute, The University of Queensland, Brisbane, Australia.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mendelson</LastName><ForeName>Michael M</ForeName><Initials>MM</Initials><AffiliationInfo><Affiliation>Framingham Heart Study, Framingham, MA, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Cardiology, Boston Children's Hospital, Boston, MA, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Müller-Nurasyid</LastName><ForeName>Martina</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Medicine I, University Hospital Munich, Campus Grosshadern, Ludwig-Maximilians-University, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Peters</LastName><ForeName>Annette</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Slagboom</LastName><ForeName>P Eline</ForeName><Initials>PE</Initials><AffiliationInfo><Affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Starr</LastName><ForeName>John M</ForeName><Initials>JM</Initials><AffiliationInfo><Affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Trégouët</LastName><ForeName>David-Alexandre</ForeName><Initials>DA</Initials><AffiliationInfo><Affiliation>Sorbonne Universités, UPMC Univ. Paris 06, INSERM, UMR_S 1166, Team Genomics & Pathophysiology of Cardiovascular Diseases, Paris, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>ICAN Institute for Cardiometabolism and Nutrition, Paris, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Uitterlinden</LastName><ForeName>André G</ForeName><Initials>AG</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Greevenbroek</LastName><ForeName>Marleen M J</ForeName><Initials>MMJ</Initials><AffiliationInfo><Affiliation>Department of Internal Medicine and School for Cardiovascular Diseases (CARIM), Maastricht University Medical Center, Maastricht, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Heemst</LastName><ForeName>Diana</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Gerontology and Geriatrics Section, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>van Iterson</LastName><ForeName>Maarten</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wells</LastName><ForeName>Philip S</ForeName><Initials>PS</Initials><AffiliationInfo><Affiliation>Department of Medicine, University of Ottawa, and the Ottawa Hospital Research Institute, Ottawa, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yao</LastName><ForeName>Chen</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Framingham Heart Study, Framingham, MA, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Deary</LastName><ForeName>Ian J</ForeName><Initials>IJ</Initials><AffiliationInfo><Affiliation>Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gagnon</LastName><ForeName>France</ForeName><Initials>F</Initials><AffiliationInfo><Affiliation>Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heijmans</LastName><ForeName>Bastiaan T</ForeName><Initials>BT</Initials><AffiliationInfo><Affiliation>Molecular Epidemiology Section, Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, The Netherlands.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Levy</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Framingham Heart Study, Framingham, MA, United States of America.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>The Population Studies Branch, National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD, United States of America.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Morange</LastName><ForeName>Pierre-Emmanuel</ForeName><Initials>PE</Initials><AffiliationInfo><Affiliation>Laboratory of Haematology, La Timone Hospital, Marseille, France.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institut National pour la Santé et la Recherche Médicale (INSERM), UMR_S 1062, Inra UMR_1260, Aix-Marseille Université, Marseille, France.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Waldenberger</LastName><ForeName>Melanie</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Research Unit of Molecular Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Heil</LastName><ForeName>Sandra G</ForeName><Initials>SG</Initials><AffiliationInfo><Affiliation>Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The 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