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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">White matter lesion progression: A genome-wide search for genetic influences</title><author><name sortKey="Hofer, Edith" sort="Hofer, Edith" uniqKey="Hofer E" first="Edith" last="Hofer">Edith Hofer</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Cavalieri, Margherita" sort="Cavalieri, Margherita" uniqKey="Cavalieri M" first="Margherita" last="Cavalieri">Margherita Cavalieri</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C" last="Bis">Joshua C. Bis</name><affiliation><nlm:aff id="A3">Cardiovascular Health Research Unit, Departments of Medicine, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Decarli, Charles" sort="Decarli, Charles" uniqKey="Decarli C" first="Charles" last="Decarli">Charles Decarli</name><affiliation><nlm:aff id="A4">Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="A5">Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Human Genetics Center, University of Texas Health Science Center, Houston, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Sigurdsson, Sigurdur" sort="Sigurdsson, Sigurdur" uniqKey="Sigurdsson S" first="Sigurdur" last="Sigurdsson">Sigurdur Sigurdsson</name><affiliation><nlm:aff id="A7">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Srikanth, Velandai" sort="Srikanth, Velandai" uniqKey="Srikanth V" first="Velandai" last="Srikanth">Velandai Srikanth</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Trompet, Stella" sort="Trompet, Stella" uniqKey="Trompet S" first="Stella" last="Trompet">Stella Trompet</name><affiliation><nlm:aff id="A9">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Verhaaren, Benjamin Fj" sort="Verhaaren, Benjamin Fj" uniqKey="Verhaaren B" first="Benjamin Fj" last="Verhaaren">Benjamin Fj Verhaaren</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wolf, Christiane" sort="Wolf, Christiane" uniqKey="Wolf C" first="Christiane" last="Wolf">Christiane Wolf</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name><affiliation><nlm:aff id="A15">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Adams, Hieab Hh" sort="Adams, Hieab Hh" uniqKey="Adams H" first="Hieab Hh" last="Adams">Hieab Hh Adams</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation><nlm:aff id="A16">INSERM U744, Pasteur Institute, Lille, France</nlm:aff></affiliation></author><author><name sortKey="Beiser, Alexa" sort="Beiser, Alexa" uniqKey="Beiser A" first="Alexa" last="Beiser">Alexa Beiser</name><affiliation><nlm:aff id="A15">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Buckley, Brendan M" sort="Buckley, Brendan M" uniqKey="Buckley B" first="Brendan M" last="Buckley">Brendan M. Buckley</name><affiliation><nlm:aff id="A17">Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland</nlm:aff></affiliation></author><author><name sortKey="Callisaya, Michele" sort="Callisaya, Michele" uniqKey="Callisaya M" first="Michele" last="Callisaya">Michele Callisaya</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Chauhan, Ganesh" sort="Chauhan, Ganesh" uniqKey="Chauhan G" first="Ganesh" last="Chauhan">Ganesh Chauhan</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A18">INSERM U1161 and Lariboisière Hospital, Paris 7 University, Paris, France</nlm:aff></affiliation></author><author><name sortKey="De Craen, Anton Jm" sort="De Craen, Anton Jm" uniqKey="De Craen A" first="Anton Jm" last="De Craen">Anton Jm De Craen</name><affiliation><nlm:aff id="A10">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Dufouil, Carole" sort="Dufouil, Carole" uniqKey="Dufouil C" first="Carole" last="Dufouil">Carole Dufouil</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Centre for Medical Systems Biology, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation><nlm:aff id="A20">Robertson Center for Biostatistics, University of Glasgow, Glasgow, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Freudenberger, Paul" sort="Freudenberger, Paul" uniqKey="Freudenberger P" first="Paul" last="Freudenberger">Paul Freudenberger</name><affiliation><nlm:aff id="A21">Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Gottesman, Rebecca F" sort="Gottesman, Rebecca F" uniqKey="Gottesman R" first="Rebecca F" last="Gottesman">Rebecca F. Gottesman</name><affiliation><nlm:aff id="A22">Department of Neurology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="A7">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A23">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Heiss, Gerardo" sort="Heiss, Gerardo" uniqKey="Heiss G" first="Gerardo" last="Heiss">Gerardo Heiss</name><affiliation><nlm:aff id="A24">Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lumley, Thomas" sort="Lumley, Thomas" uniqKey="Lumley T" first="Thomas" last="Lumley">Thomas Lumley</name><affiliation><nlm:aff id="A25">Department of Statistics, University of Auckland, Auckland, New Zealand</nlm:aff></affiliation></author><author><name sortKey="Martinez, Oliver" sort="Martinez, Oliver" uniqKey="Martinez O" first="Oliver" last="Martinez">Oliver Martinez</name><affiliation><nlm:aff id="A4">Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Mazoyer, Bernard" sort="Mazoyer, Bernard" uniqKey="Mazoyer B" first="Bernard" last="Mazoyer">Bernard Mazoyer</name><affiliation><nlm:aff id="A26">CNRS-CEA UMR5296, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Moran, Chris" sort="Moran, Chris" uniqKey="Moran C" first="Chris" last="Moran">Chris Moran</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Niessen, Wiro J" sort="Niessen, Wiro J" uniqKey="Niessen W" first="Wiro J." last="Niessen">Wiro J. Niessen</name><affiliation><nlm:aff id="A27">Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Faculty of Applied Sciences, Delft University, Delft, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Phan, Thanh" sort="Phan, Thanh" uniqKey="Phan T" first="Thanh" last="Phan">Thanh Phan</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M" last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="A3">Cardiovascular Health Research Unit, Departments of Medicine, University of Washington, Seattle, WA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Satizabal, Claudia L" sort="Satizabal, Claudia L" uniqKey="Satizabal C" first="Claudia L" last="Satizabal">Claudia L. Satizabal</name><affiliation><nlm:aff id="A30">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Sattar, Naveed" sort="Sattar, Naveed" uniqKey="Sattar N" first="Naveed" last="Sattar">Naveed Sattar</name><affiliation><nlm:aff id="A31">Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, Glasgow, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Schilling, Sabrina" sort="Schilling, Sabrina" uniqKey="Schilling S" first="Sabrina" last="Schilling">Sabrina Schilling</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A18">INSERM U1161 and Lariboisière Hospital, Paris 7 University, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Shibata, Dean K" sort="Shibata, Dean K" uniqKey="Shibata D" first="Dean K" last="Shibata">Dean K. Shibata</name><affiliation><nlm:aff id="A32">Department of Radiology, University of Washington, Seattle, WA, USA</nlm:aff></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:aff id="A33">Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert" sort="Smith, Albert" uniqKey="Smith A" first="Albert" last="Smith">Albert Smith</name><affiliation><nlm:aff id="A7">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A23">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Stott, David J" sort="Stott, David J" uniqKey="Stott D" first="David J" last="Stott">David J. Stott</name><affiliation><nlm:aff id="A31">Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, Glasgow, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Taylor, Kent D" sort="Taylor, Kent D" uniqKey="Taylor K" first="Kent D" last="Taylor">Kent D. Taylor</name><affiliation><nlm:aff id="A34">Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Los Angeles, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Thomson, Russell" sort="Thomson, Russell" uniqKey="Thomson R" first="Russell" last="Thomson">Russell Thomson</name><affiliation><nlm:aff id="A36">Menzies Research Institute, Hobart, Tasmania, Australia</nlm:aff></affiliation></author><author><name sortKey="Toglhofer, Anna M" sort="Toglhofer, Anna M" uniqKey="Toglhofer A" first="Anna M" last="Töglhofer">Anna M. Töglhofer</name><affiliation><nlm:aff id="A21">Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name><affiliation><nlm:aff id="A37">INSERM U708, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Van Buchem, Mark" sort="Van Buchem, Mark" uniqKey="Van Buchem M" first="Mark" last="Van Buchem">Mark Van Buchem</name><affiliation><nlm:aff id="A38">Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name><affiliation><nlm:aff id="A15">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Westendorp, Rudi Gj" sort="Westendorp, Rudi Gj" uniqKey="Westendorp R" first="Rudi Gj" last="Westendorp">Rudi Gj Westendorp</name><affiliation><nlm:aff id="A10">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Public Health, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Windham, B Gwen" sort="Windham, B Gwen" uniqKey="Windham B" first="B Gwen" last="Windham">B Gwen Windham</name><affiliation><nlm:aff id="A40">Department of Medicine, University of Mississippi, Jackson, MS, USA</nlm:aff></affiliation></author><author><name sortKey="Vernooij, Meike W" sort="Vernooij, Meike W" uniqKey="Vernooij M" first="Meike W" last="Vernooij">Meike W. Vernooij</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zijdenbos, Alex" sort="Zijdenbos, Alex" uniqKey="Zijdenbos A" first="Alex" last="Zijdenbos">Alex Zijdenbos</name><affiliation><nlm:aff id="A41">Biospective Inc., Montréal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Beare, Richard" sort="Beare, Richard" uniqKey="Beare R" first="Richard" last="Beare">Richard Beare</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Developmental Imaging, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stéphanie" last="Debette">Stéphanie Debette</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A18">INSERM U1161 and Lariboisière Hospital, Paris 7 University, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff></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:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J Wouter" last="Jukema">J Wouter Jukema</name><affiliation><nlm:aff id="A9">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A44">Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J" last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="A45">National Institute on Aging, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Longstreth, W T" sort="Longstreth, W T" uniqKey="Longstreth W" first="W T" last="Longstreth">W T Longstreth</name><affiliation><nlm:aff id="A46">Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Mosley, Thomas H" sort="Mosley, Thomas H" uniqKey="Mosley T" first="Thomas H" last="Mosley">Thomas H. Mosley</name><affiliation><nlm:aff id="A40">Department of Medicine, University of Mississippi, Jackson, MS, USA</nlm:aff></affiliation></author><author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name><affiliation><nlm:aff id="A30">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Helena" sort="Schmidt, Helena" uniqKey="Schmidt H" first="Helena" last="Schmidt">Helena Schmidt</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Reinhold" sort="Schmidt, Reinhold" uniqKey="Schmidt R" first="Reinhold" last="Schmidt">Reinhold Schmidt</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">26451028</idno><idno type="pmc">4749149</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4749149</idno><idno type="RBID">PMC:4749149</idno><idno type="doi">10.1161/STROKEAHA.115.009252</idno><date when="2015">2015</date><idno type="wicri:Area/Pmc/Corpus">001C76</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001C76</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">White matter lesion progression: A genome-wide search for genetic influences</title><author><name sortKey="Hofer, Edith" sort="Hofer, Edith" uniqKey="Hofer E" first="Edith" last="Hofer">Edith Hofer</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="A2">Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Cavalieri, Margherita" sort="Cavalieri, Margherita" uniqKey="Cavalieri M" first="Margherita" last="Cavalieri">Margherita Cavalieri</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C" last="Bis">Joshua C. Bis</name><affiliation><nlm:aff id="A3">Cardiovascular Health Research Unit, Departments of Medicine, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Decarli, Charles" sort="Decarli, Charles" uniqKey="Decarli C" first="Charles" last="Decarli">Charles Decarli</name><affiliation><nlm:aff id="A4">Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name><affiliation><nlm:aff id="A5">Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A6">Human Genetics Center, University of Texas Health Science Center, Houston, TX, USA</nlm:aff></affiliation></author><author><name sortKey="Sigurdsson, Sigurdur" sort="Sigurdsson, Sigurdur" uniqKey="Sigurdsson S" first="Sigurdur" last="Sigurdsson">Sigurdur Sigurdsson</name><affiliation><nlm:aff id="A7">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation></author><author><name sortKey="Srikanth, Velandai" sort="Srikanth, Velandai" uniqKey="Srikanth V" first="Velandai" last="Srikanth">Velandai Srikanth</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Trompet, Stella" sort="Trompet, Stella" uniqKey="Trompet S" first="Stella" last="Trompet">Stella Trompet</name><affiliation><nlm:aff id="A9">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A10">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Verhaaren, Benjamin Fj" sort="Verhaaren, Benjamin Fj" uniqKey="Verhaaren B" first="Benjamin Fj" last="Verhaaren">Benjamin Fj Verhaaren</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wolf, Christiane" sort="Wolf, Christiane" uniqKey="Wolf C" first="Christiane" last="Wolf">Christiane Wolf</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A14">Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany</nlm:aff></affiliation></author><author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name><affiliation><nlm:aff id="A15">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Adams, Hieab Hh" sort="Adams, Hieab Hh" uniqKey="Adams H" first="Hieab Hh" last="Adams">Hieab Hh Adams</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name><affiliation><nlm:aff id="A16">INSERM U744, Pasteur Institute, Lille, France</nlm:aff></affiliation></author><author><name sortKey="Beiser, Alexa" sort="Beiser, Alexa" uniqKey="Beiser A" first="Alexa" last="Beiser">Alexa Beiser</name><affiliation><nlm:aff id="A15">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Buckley, Brendan M" sort="Buckley, Brendan M" uniqKey="Buckley B" first="Brendan M" last="Buckley">Brendan M. Buckley</name><affiliation><nlm:aff id="A17">Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland</nlm:aff></affiliation></author><author><name sortKey="Callisaya, Michele" sort="Callisaya, Michele" uniqKey="Callisaya M" first="Michele" last="Callisaya">Michele Callisaya</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Chauhan, Ganesh" sort="Chauhan, Ganesh" uniqKey="Chauhan G" first="Ganesh" last="Chauhan">Ganesh Chauhan</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A18">INSERM U1161 and Lariboisière Hospital, Paris 7 University, Paris, France</nlm:aff></affiliation></author><author><name sortKey="De Craen, Anton Jm" sort="De Craen, Anton Jm" uniqKey="De Craen A" first="Anton Jm" last="De Craen">Anton Jm De Craen</name><affiliation><nlm:aff id="A10">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Dufouil, Carole" sort="Dufouil, Carole" uniqKey="Dufouil C" first="Carole" last="Dufouil">Carole Dufouil</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Van Duijn, Cornelia M" sort="Van Duijn, Cornelia M" uniqKey="Van Duijn C" first="Cornelia M" last="Van Duijn">Cornelia M. Van Duijn</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A19">Centre for Medical Systems Biology, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Ford, Ian" sort="Ford, Ian" uniqKey="Ford I" first="Ian" last="Ford">Ian Ford</name><affiliation><nlm:aff id="A20">Robertson Center for Biostatistics, University of Glasgow, Glasgow, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Freudenberger, Paul" sort="Freudenberger, Paul" uniqKey="Freudenberger P" first="Paul" last="Freudenberger">Paul Freudenberger</name><affiliation><nlm:aff id="A21">Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Gottesman, Rebecca F" sort="Gottesman, Rebecca F" uniqKey="Gottesman R" first="Rebecca F" last="Gottesman">Rebecca F. Gottesman</name><affiliation><nlm:aff id="A22">Department of Neurology, Johns Hopkins University, Baltimore, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name><affiliation><nlm:aff id="A7">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A23">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Heiss, Gerardo" sort="Heiss, Gerardo" uniqKey="Heiss G" first="Gerardo" last="Heiss">Gerardo Heiss</name><affiliation><nlm:aff id="A24">Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA</nlm:aff></affiliation></author><author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Lumley, Thomas" sort="Lumley, Thomas" uniqKey="Lumley T" first="Thomas" last="Lumley">Thomas Lumley</name><affiliation><nlm:aff id="A25">Department of Statistics, University of Auckland, Auckland, New Zealand</nlm:aff></affiliation></author><author><name sortKey="Martinez, Oliver" sort="Martinez, Oliver" uniqKey="Martinez O" first="Oliver" last="Martinez">Oliver Martinez</name><affiliation><nlm:aff id="A4">Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Mazoyer, Bernard" sort="Mazoyer, Bernard" uniqKey="Mazoyer B" first="Bernard" last="Mazoyer">Bernard Mazoyer</name><affiliation><nlm:aff id="A26">CNRS-CEA UMR5296, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Moran, Chris" sort="Moran, Chris" uniqKey="Moran C" first="Chris" last="Moran">Chris Moran</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Niessen, Wiro J" sort="Niessen, Wiro J" uniqKey="Niessen W" first="Wiro J." last="Niessen">Wiro J. Niessen</name><affiliation><nlm:aff id="A27">Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A28">Faculty of Applied Sciences, Delft University, Delft, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Phan, Thanh" sort="Phan, Thanh" uniqKey="Phan T" first="Thanh" last="Phan">Thanh Phan</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Psaty, Bruce M" sort="Psaty, Bruce M" uniqKey="Psaty B" first="Bruce M" last="Psaty">Bruce M. Psaty</name><affiliation><nlm:aff id="A3">Cardiovascular Health Research Unit, Departments of Medicine, University of Washington, Seattle, WA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A29">Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Satizabal, Claudia L" sort="Satizabal, Claudia L" uniqKey="Satizabal C" first="Claudia L" last="Satizabal">Claudia L. Satizabal</name><affiliation><nlm:aff id="A30">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Sattar, Naveed" sort="Sattar, Naveed" uniqKey="Sattar N" first="Naveed" last="Sattar">Naveed Sattar</name><affiliation><nlm:aff id="A31">Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, Glasgow, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Schilling, Sabrina" sort="Schilling, Sabrina" uniqKey="Schilling S" first="Sabrina" last="Schilling">Sabrina Schilling</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A18">INSERM U1161 and Lariboisière Hospital, Paris 7 University, Paris, France</nlm:aff></affiliation></author><author><name sortKey="Shibata, Dean K" sort="Shibata, Dean K" uniqKey="Shibata D" first="Dean K" last="Shibata">Dean K. Shibata</name><affiliation><nlm:aff id="A32">Department of Radiology, University of Washington, Seattle, WA, USA</nlm:aff></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:aff id="A33">Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Smith, Albert" sort="Smith, Albert" uniqKey="Smith A" first="Albert" last="Smith">Albert Smith</name><affiliation><nlm:aff id="A7">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff></affiliation><affiliation><nlm:aff id="A23">University of Iceland, Reykjavik, Iceland</nlm:aff></affiliation></author><author><name sortKey="Stott, David J" sort="Stott, David J" uniqKey="Stott D" first="David J" last="Stott">David J. Stott</name><affiliation><nlm:aff id="A31">Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, Glasgow, United Kingdom</nlm:aff></affiliation></author><author><name sortKey="Taylor, Kent D" sort="Taylor, Kent D" uniqKey="Taylor K" first="Kent D" last="Taylor">Kent D. Taylor</name><affiliation><nlm:aff id="A34">Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Los Angeles, CA, USA</nlm:aff></affiliation><affiliation><nlm:aff id="A35">Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA</nlm:aff></affiliation></author><author><name sortKey="Thomson, Russell" sort="Thomson, Russell" uniqKey="Thomson R" first="Russell" last="Thomson">Russell Thomson</name><affiliation><nlm:aff id="A36">Menzies Research Institute, Hobart, Tasmania, Australia</nlm:aff></affiliation></author><author><name sortKey="Toglhofer, Anna M" sort="Toglhofer, Anna M" uniqKey="Toglhofer A" first="Anna M" last="Töglhofer">Anna M. Töglhofer</name><affiliation><nlm:aff id="A21">Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name><affiliation><nlm:aff id="A37">INSERM U708, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation></author><author><name sortKey="Van Buchem, Mark" sort="Van Buchem, Mark" uniqKey="Van Buchem M" first="Mark" last="Van Buchem">Mark Van Buchem</name><affiliation><nlm:aff id="A38">Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name><affiliation><nlm:aff id="A15">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Westendorp, Rudi Gj" sort="Westendorp, Rudi Gj" uniqKey="Westendorp R" first="Rudi Gj" last="Westendorp">Rudi Gj Westendorp</name><affiliation><nlm:aff id="A10">Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A39">Department of Public Health, University of Copenhagen, Copenhagen, Denmark</nlm:aff></affiliation></author><author><name sortKey="Windham, B Gwen" sort="Windham, B Gwen" uniqKey="Windham B" first="B Gwen" last="Windham">B Gwen Windham</name><affiliation><nlm:aff id="A40">Department of Medicine, University of Mississippi, Jackson, MS, USA</nlm:aff></affiliation></author><author><name sortKey="Vernooij, Meike W" sort="Vernooij, Meike W" uniqKey="Vernooij M" first="Meike W" last="Vernooij">Meike W. Vernooij</name><affiliation><nlm:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Zijdenbos, Alex" sort="Zijdenbos, Alex" uniqKey="Zijdenbos A" first="Alex" last="Zijdenbos">Alex Zijdenbos</name><affiliation><nlm:aff id="A41">Biospective Inc., Montréal, Quebec, Canada</nlm:aff></affiliation></author><author><name sortKey="Beare, Richard" sort="Beare, Richard" uniqKey="Beare R" first="Richard" last="Beare">Richard Beare</name><affiliation><nlm:aff id="A8">Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</nlm:aff></affiliation><affiliation><nlm:aff id="A42">Developmental Imaging, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, Victoria, Australia</nlm:aff></affiliation></author><author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stéphanie" last="Debette">Stéphanie Debette</name><affiliation><nlm:aff id="A13">INSERM U897, Université Bordeaux Segalen, Bordeaux, France</nlm:aff></affiliation><affiliation><nlm:aff id="A18">INSERM U1161 and Lariboisière Hospital, Paris 7 University, Paris, France</nlm:aff></affiliation><affiliation><nlm:aff id="A30">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff></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:aff id="A11">Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A12">Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Jukema, J Wouter" sort="Jukema, J Wouter" uniqKey="Jukema J" first="J Wouter" last="Jukema">J Wouter Jukema</name><affiliation><nlm:aff id="A9">Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A43">Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</nlm:aff></affiliation><affiliation><nlm:aff id="A44">Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</nlm:aff></affiliation></author><author><name sortKey="Launer, Lenore J" sort="Launer, Lenore J" uniqKey="Launer L" first="Lenore J" last="Launer">Lenore J. Launer</name><affiliation><nlm:aff id="A45">National Institute on Aging, Bethesda, MD, USA</nlm:aff></affiliation></author><author><name sortKey="Longstreth, W T" sort="Longstreth, W T" uniqKey="Longstreth W" first="W T" last="Longstreth">W T Longstreth</name><affiliation><nlm:aff id="A46">Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, USA</nlm:aff></affiliation></author><author><name sortKey="Mosley, Thomas H" sort="Mosley, Thomas H" uniqKey="Mosley T" first="Thomas H" last="Mosley">Thomas H. Mosley</name><affiliation><nlm:aff id="A40">Department of Medicine, University of Mississippi, Jackson, MS, USA</nlm:aff></affiliation></author><author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name><affiliation><nlm:aff id="A30">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Helena" sort="Schmidt, Helena" uniqKey="Schmidt H" first="Helena" last="Schmidt">Helena Schmidt</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation><affiliation><nlm:aff id="A21">Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author><author><name sortKey="Schmidt, Reinhold" sort="Schmidt, Reinhold" uniqKey="Schmidt R" first="Reinhold" last="Schmidt">Reinhold Schmidt</name><affiliation><nlm:aff id="A1">Department of Neurology, Medical University of Graz, Graz, Austria</nlm:aff></affiliation></author></analytic><series><title level="j">Stroke; a journal of cerebral circulation</title><idno type="ISSN">0039-2499</idno><idno type="eISSN">1524-4628</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background and Purpose</title><p id="P1">White matter lesion (WML) progression on magnetic resonance imaging (MRI) is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in seven cohorts risk models including demographics, vascular risk factors plus single nucleotide polymorphisms (SNPs) that have been shown to be associated cross-sectionally with WML in the current and previous association studies.</p></sec><sec id="S3"><title>Results</title><p id="P3">A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no SNPs achieved genome-wide significance (p-value < 5×10<sup>−8</sup>). Four loci were suggestive (p-value < 1×10<sup>−5</sup>) of an association with WML progression: 10q24.32 (rs10883817, p=1.46×10<sup>−6</sup>); 12q13.13 (rs4761974, p=8.71×10<sup>−7</sup>); 20p12.1 (rs6135309, p=3.69×10<sup>−6</sup>); and 4p15.31 (rs7664442, p=2.26×10<sup>−6</sup>). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors and baseline WML burden.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, life-style or host-related biological factors.</p></sec></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<pmc-dir>properties manuscript</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-journal-id">0235266</journal-id><journal-id journal-id-type="pubmed-jr-id">7613</journal-id><journal-id journal-id-type="nlm-ta">Stroke</journal-id><journal-id journal-id-type="iso-abbrev">Stroke</journal-id><journal-title-group><journal-title>Stroke; a journal of cerebral circulation</journal-title></journal-title-group><issn pub-type="ppub">0039-2499</issn><issn pub-type="epub">1524-4628</issn></journal-meta><article-meta><article-id pub-id-type="pmid">26451028</article-id><article-id pub-id-type="pmc">4749149</article-id><article-id pub-id-type="doi">10.1161/STROKEAHA.115.009252</article-id><article-id pub-id-type="manuscript">NIHMS757019</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>White matter lesion progression: A genome-wide search for genetic influences</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Hofer</surname><given-names>Edith</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A2">2</xref></contrib><contrib contrib-type="author"><name><surname>Cavalieri</surname><given-names>Margherita</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bis</surname><given-names>Joshua C</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A3">3</xref></contrib><contrib contrib-type="author"><name><surname>DeCarli</surname><given-names>Charles</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Fornage</surname><given-names>Myriam</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A5">5</xref><xref ref-type="aff" rid="A6">6</xref></contrib><contrib contrib-type="author"><name><surname>Sigurdsson</surname><given-names>Sigurdur</given-names></name><degrees>MSc</degrees><xref ref-type="aff" rid="A7">7</xref></contrib><contrib contrib-type="author"><name><surname>Srikanth</surname><given-names>Velandai</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Trompet</surname><given-names>Stella</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Verhaaren</surname><given-names>Benjamin FJ</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Wolf</surname><given-names>Christiane</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A14">14</xref></contrib><contrib contrib-type="author"><name><surname>Yang</surname><given-names>Qiong</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Adams</surname><given-names>Hieab HH</given-names></name><degrees>MSc</degrees><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Amouyel</surname><given-names>Philippe</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A16">16</xref></contrib><contrib contrib-type="author"><name><surname>Beiser</surname><given-names>Alexa</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Buckley</surname><given-names>Brendan M</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A17">17</xref></contrib><contrib contrib-type="author"><name><surname>Callisaya</surname><given-names>Michele</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Chauhan</surname><given-names>Ganesh</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>de Craen</surname><given-names>Anton JM</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A10">10</xref></contrib><contrib contrib-type="author"><name><surname>Dufouil</surname><given-names>Carole</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A13">13</xref></contrib><contrib contrib-type="author"><name><surname>van Duijn</surname><given-names>Cornelia M</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A19">19</xref></contrib><contrib 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contrib-type="author"><name><surname>Hofman</surname><given-names>Albert</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A11">11</xref></contrib><contrib contrib-type="author"><name><surname>Lumley</surname><given-names>Thomas</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A25">25</xref></contrib><contrib contrib-type="author"><name><surname>Martinez</surname><given-names>Oliver</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A4">4</xref></contrib><contrib contrib-type="author"><name><surname>Mazoyer</surname><given-names>Bernard</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A26">26</xref></contrib><contrib contrib-type="author"><name><surname>Moran</surname><given-names>Chris</given-names></name><degrees>MB BCh</degrees><xref ref-type="aff" rid="A8">8</xref></contrib><contrib contrib-type="author"><name><surname>Niessen</surname><given-names>Wiro J.</given-names></name><degrees>PhD</degrees><xref 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rid="A13">13</xref><xref ref-type="aff" rid="A18">18</xref></contrib><contrib contrib-type="author"><name><surname>Shibata</surname><given-names>Dean K</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A32">32</xref></contrib><contrib contrib-type="author"><name><surname>Slagboom</surname><given-names>P Eline</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A33">33</xref></contrib><contrib contrib-type="author"><name><surname>Smith</surname><given-names>Albert</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A7">7</xref><xref ref-type="aff" rid="A23">23</xref></contrib><contrib contrib-type="author"><name><surname>Stott</surname><given-names>David J</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A31">31</xref></contrib><contrib contrib-type="author"><name><surname>Taylor</surname><given-names>Kent D</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A34">34</xref><xref ref-type="aff" rid="A35">35</xref></contrib><contrib contrib-type="author"><name><surname>Thomson</surname><given-names>Russell</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A36">36</xref></contrib><contrib contrib-type="author"><name><surname>Töglhofer</surname><given-names>Anna M</given-names></name><degrees>MSc</degrees><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Tzourio</surname><given-names>Christophe</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A37">37</xref></contrib><contrib contrib-type="author"><name><surname>van Buchem</surname><given-names>Mark</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A38">38</xref></contrib><contrib contrib-type="author"><name><surname>Wang</surname><given-names>Jing</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A15">15</xref></contrib><contrib contrib-type="author"><name><surname>Westendorp</surname><given-names>Rudi GJ</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A10">10</xref><xref ref-type="aff" rid="A39">39</xref></contrib><contrib contrib-type="author"><name><surname>Windham</surname><given-names>B Gwen</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Vernooij</surname><given-names>Meike W</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Zijdenbos</surname><given-names>Alex</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A41">41</xref></contrib><contrib contrib-type="author"><name><surname>Beare</surname><given-names>Richard</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A8">8</xref><xref ref-type="aff" rid="A42">42</xref></contrib><contrib contrib-type="author"><name><surname>Debette</surname><given-names>Stéphanie</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A13">13</xref><xref ref-type="aff" rid="A18">18</xref><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Ikram</surname><given-names>M Arfan</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A11">11</xref><xref ref-type="aff" rid="A12">12</xref></contrib><contrib contrib-type="author"><name><surname>Jukema</surname><given-names>J Wouter</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A9">9</xref><xref ref-type="aff" rid="A43">43</xref><xref ref-type="aff" rid="A44">44</xref></contrib><contrib contrib-type="author"><name><surname>Launer</surname><given-names>Lenore J</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A45">45</xref></contrib><contrib contrib-type="author"><name><surname>Longstreth</surname><given-names>W T</given-names><suffix>Jr</suffix></name><degrees>MD</degrees><xref ref-type="aff" rid="A46">46</xref></contrib><contrib contrib-type="author"><name><surname>Mosley</surname><given-names>Thomas H</given-names></name><degrees>PhD</degrees><xref ref-type="aff" rid="A40">40</xref></contrib><contrib contrib-type="author"><name><surname>Seshadri</surname><given-names>Sudha</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A30">30</xref></contrib><contrib contrib-type="author"><name><surname>Schmidt</surname><given-names>Helena</given-names></name><degrees>MD PhD</degrees><xref ref-type="aff" rid="A1">1</xref><xref ref-type="aff" rid="A21">21</xref></contrib><contrib contrib-type="author"><name><surname>Schmidt</surname><given-names>Reinhold</given-names></name><degrees>MD</degrees><xref ref-type="aff" rid="A1">1</xref></contrib><on-behalf-of>on behalf of the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium</on-behalf-of></contrib-group><aff id="A1"><label>1</label>Department of Neurology, Medical University of Graz, Graz, Austria</aff><aff id="A2"><label>2</label>Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria</aff><aff id="A3"><label>3</label>Cardiovascular Health Research Unit, Departments of Medicine, University of Washington, Seattle, WA, USA</aff><aff id="A4"><label>4</label>Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA</aff><aff id="A5"><label>5</label>Brown Foundation Institute of Molecular Medicine, University of Texas Health Science Center, Houston, TX, USA</aff><aff id="A6"><label>6</label>Human Genetics Center, University of Texas Health Science Center, Houston, TX, USA</aff><aff id="A7"><label>7</label>Icelandic Heart Association, Kopavogur, Iceland</aff><aff id="A8"><label>8</label>Stroke and Ageing Research Group, Department of Medicine, Southern Clinical School, Monash University, Melbourne, Victoria, Australia</aff><aff id="A9"><label>9</label>Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A10"><label>10</label>Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A11"><label>11</label>Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A12"><label>12</label>Department of Radiology, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A13"><label>13</label>INSERM U897, Université Bordeaux Segalen, Bordeaux, France</aff><aff id="A14"><label>14</label>Department of Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany</aff><aff id="A15"><label>15</label>Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</aff><aff id="A16"><label>16</label>INSERM U744, Pasteur Institute, Lille, France</aff><aff id="A17"><label>17</label>Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland</aff><aff id="A18"><label>18</label>INSERM U1161 and Lariboisière Hospital, Paris 7 University, Paris, France</aff><aff id="A19"><label>19</label>Centre for Medical Systems Biology, Leiden, The Netherlands</aff><aff id="A20"><label>20</label>Robertson Center for Biostatistics, University of Glasgow, Glasgow, United Kingdom</aff><aff id="A21"><label>21</label>Research Unit for Genetic Epidemiology, Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University of Graz, Graz, Austria</aff><aff id="A22"><label>22</label>Department of Neurology, Johns Hopkins University, Baltimore, MD, USA</aff><aff id="A23"><label>23</label>University of Iceland, Reykjavik, Iceland</aff><aff id="A24"><label>24</label>Department of Epidemiology, University of North Carolina, Chapel Hill, NC, USA</aff><aff id="A25"><label>25</label>Department of Statistics, University of Auckland, Auckland, New Zealand</aff><aff id="A26"><label>26</label>CNRS-CEA UMR5296, Université Bordeaux Segalen, Bordeaux, France</aff><aff id="A27"><label>27</label>Department of Medical Informatics, Erasmus Medical Center, Rotterdam, The Netherlands</aff><aff id="A28"><label>28</label>Faculty of Applied Sciences, Delft University, Delft, The Netherlands</aff><aff id="A29"><label>29</label>Group Health Research Institute, Group Health Cooperative, Seattle, WA, USA</aff><aff id="A30"><label>30</label>Department of Neurology, Boston University School of Medicine, Boston, MA, USA</aff><aff id="A31"><label>31</label>Institute of Cardiovascular and Medical Sciences, Faculty of Medicine, Glasgow, United Kingdom</aff><aff id="A32"><label>32</label>Department of Radiology, University of Washington, Seattle, WA, USA</aff><aff id="A33"><label>33</label>Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A34"><label>34</label>Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute, Los Angeles, CA, USA</aff><aff id="A35"><label>35</label>Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA</aff><aff id="A36"><label>36</label>Menzies Research Institute, Hobart, Tasmania, Australia</aff><aff id="A37"><label>37</label>INSERM U708, Université Bordeaux Segalen, Bordeaux, France</aff><aff id="A38"><label>38</label>Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands</aff><aff id="A39"><label>39</label>Department of Public Health, University of Copenhagen, Copenhagen, Denmark</aff><aff id="A40"><label>40</label>Department of Medicine, University of Mississippi, Jackson, MS, USA</aff><aff id="A41"><label>41</label>Biospective Inc., Montréal, Quebec, Canada</aff><aff id="A42"><label>42</label>Developmental Imaging, Murdoch Childrens Research Institute, Royal Childrens Hospital, Parkville, Victoria, Australia</aff><aff id="A43"><label>43</label>Durrer Center for Cardiogenetic Research, Amsterdam, The Netherlands</aff><aff id="A44"><label>44</label>Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands</aff><aff id="A45"><label>45</label>National Institute on Aging, Bethesda, MD, USA</aff><aff id="A46"><label>46</label>Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, USA</aff><author-notes><corresp id="CR1"><bold>Corresponding author:</bold> Reinhold Schmidt, Medical University of Graz, Department of Neurology, Division of Neurogeriatrics, Auenbruggerplatz 22, 8036 Graz, Austria, Fax: +43 316 385 14178, Phone: +43 316 385 13136, <email>reinhold.schmidt@medunigraz.at</email></corresp></author-notes><pub-date pub-type="nihms-submitted"><day>5</day><month>2</month><year>2016</year></pub-date><pub-date pub-type="epub"><day>08</day><month>10</month><year>2015</year></pub-date><pub-date pub-type="ppub"><month>11</month><year>2015</year></pub-date><pub-date pub-type="pmc-release"><day>10</day><month>2</month><year>2016</year></pub-date><volume>46</volume><issue>11</issue><fpage>3048</fpage><lpage>3057</lpage><pmc-comment>elocation-id from pubmed: 10.1161/STROKEAHA.115.009252</pmc-comment>
<abstract><sec id="S1"><title>Background and Purpose</title><p id="P1">White matter lesion (WML) progression on magnetic resonance imaging (MRI) is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium.</p></sec><sec id="S2"><title>Methods</title><p id="P2">Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in seven cohorts risk models including demographics, vascular risk factors plus single nucleotide polymorphisms (SNPs) that have been shown to be associated cross-sectionally with WML in the current and previous association studies.</p></sec><sec id="S3"><title>Results</title><p id="P3">A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5%, and no SNPs achieved genome-wide significance (p-value < 5×10<sup>−8</sup>). Four loci were suggestive (p-value < 1×10<sup>−5</sup>) of an association with WML progression: 10q24.32 (rs10883817, p=1.46×10<sup>−6</sup>); 12q13.13 (rs4761974, p=8.71×10<sup>−7</sup>); 20p12.1 (rs6135309, p=3.69×10<sup>−6</sup>); and 4p15.31 (rs7664442, p=2.26×10<sup>−6</sup>). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors and baseline WML burden.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, life-style or host-related biological factors.</p></sec></abstract><kwd-group><kwd>magnetic resonance imaging</kwd><kwd>aging</kwd><kwd>cerebral small vessel disease</kwd></kwd-group></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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