Common variants at 6q22 and 17q21 are associated with intracranial volume
Identifieur interne : 000D76 ( Ncbi/Merge ); précédent : 000D75; suivant : 000D77Common variants at 6q22 and 17q21 are associated with intracranial volume
Auteurs : M. Arfan Ikram [Pays-Bas] ; Myriam Fornage [États-Unis] ; Albert V. Smith [Islande] ; Sudha Seshadri [États-Unis] ; Reinhold Schmidt [Autriche] ; Stéphanie Debette [États-Unis, France] ; Henri A. Vrooman [Pays-Bas] ; Sigurdur Sigurdsson [Islande] ; Stefan Ropele [Autriche] ; H. Rob Taal [Pays-Bas] ; Dennis O. Mook-Kanamori [Pays-Bas, Qatar] ; Laura H. Coker [États-Unis] ; W. T. Longstreth [États-Unis] ; Wiro J. Niessen [Pays-Bas] ; Anita L. Destefano [États-Unis] ; Alexa Beiser [États-Unis] ; Alex P. Zijdenbos [Canada] ; Maksim Struchalin [Pays-Bas] ; Clifford R. Jack [États-Unis] ; Fernando Rivadeneira [Pays-Bas] ; Andre G. Uitterlinden [Pays-Bas] ; David S. Knopman [États-Unis] ; Anna-Liisa Hartikainen [Finlande] ; Craig E. Pennell [Australie] ; Elisabeth Thiering [Allemagne] ; Eric A. P. Steegers [Pays-Bas] ; Hakon Hakonarson [États-Unis] ; Joachim Heinrich [Australie] ; Lyle J. Palmer [Canada] ; Marjo-Riitta Jarvelin [Royaume-Uni, Finlande] ; Mark I. Mccarthy [Royaume-Uni] ; Struan F. A. Grant [États-Unis] ; Beate St Pourcain [Royaume-Uni] ; Nicholas J. Timpson [Royaume-Uni] ; George Davey Smith [Royaume-Uni] ; Ulla Sovio [Royaume-Uni] ; Mike A. Nalls [États-Unis] ; Rhoda Au [États-Unis, Autriche] ; Albert Hofman [Pays-Bas] ; Haukur Gudnason [Islande] ; Aad Van Der Lugt [Pays-Bas] ; Tamara B. Harris [États-Unis] ; William M. Meeks [États-Unis] ; Meike W. Vernooij [Pays-Bas] ; Mark A. Van Buchem [Pays-Bas] ; Diane Catellier [États-Unis] ; Vincent W. V. Jaddoe [Pays-Bas] ; Vilmundur Gudnason [Islande] ; B. Gwen Windham [États-Unis] ; Philip A. Wolf [États-Unis] ; Cornelia M. Van Duijn [Pays-Bas] ; Thomas H. Mosley [États-Unis] ; Helena Schmidt [Autriche] ; Lenore J. Launer [États-Unis] ; Monique M. B. Breteler [Pays-Bas, Allemagne] ; Charles Decarli [États-Unis]Source :
- Nature genetics [ 1061-4036 ] ; 2012.
Abstract
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study in 8,175 community-dwelling elderly did not reveal any genome-wide significant associations (p<5*10−8) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (p=3.4*10−11), a known height locus on chromosome 6q22, and rs9915547, tagging the inversion on chromosome 17q21 (p=1.5*10−12). We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 older persons (p=1.1*10−3 for 6q22 and p=1.2*10−3 for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age 14.5 months). Our data identify two loci associated with head size, with the inversion on 17q21 also likely involved in attaining maximal brain size.
Url:
DOI: 10.1038/ng.2245
PubMed: 22504418
PubMed Central: 3618290
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<author><name sortKey="Taal, H Rob" sort="Taal, H Rob" uniqKey="Taal H" first="H. Rob" last="Taal">H. Rob Taal</name>
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<author><name sortKey="Coker, Laura H" sort="Coker, Laura H" uniqKey="Coker L" first="Laura H." last="Coker">Laura H. Coker</name>
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<author><name sortKey="Niessen, Wiro J" sort="Niessen, Wiro J" uniqKey="Niessen W" first="Wiro J." last="Niessen">Wiro J. Niessen</name>
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<author><name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita L." last="Destefano">Anita L. Destefano</name>
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<affiliation wicri:level="2"><nlm:aff id="A8">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff>
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<wicri:regionArea>Department of Biostatistics, Boston University School of Public Health, Boston, MA</wicri:regionArea>
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<affiliation wicri:level="2"><nlm:aff id="A9">The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
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<author><name sortKey="Beiser, Alexa" sort="Beiser, Alexa" uniqKey="Beiser A" first="Alexa" last="Beiser">Alexa Beiser</name>
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<affiliation wicri:level="2"><nlm:aff id="A8">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff>
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<affiliation wicri:level="2"><nlm:aff id="A9">The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
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<author><name sortKey="Zijdenbos, Alex P" sort="Zijdenbos, Alex P" uniqKey="Zijdenbos A" first="Alex P." last="Zijdenbos">Alex P. Zijdenbos</name>
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<author><name sortKey="Struchalin, Maksim" sort="Struchalin, Maksim" uniqKey="Struchalin M" first="Maksim" last="Struchalin">Maksim Struchalin</name>
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<author><name sortKey="Jack, Clifford R" sort="Jack, Clifford R" uniqKey="Jack C" first="Clifford R." last="Jack">Clifford R. Jack</name>
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<author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name>
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<affiliation wicri:level="3"><nlm:aff id="A21">Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
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<author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
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<affiliation wicri:level="3"><nlm:aff id="A21">Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
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<author><name sortKey="Knopman, David S" sort="Knopman, David S" uniqKey="Knopman D" first="David S." last="Knopman">David S. Knopman</name>
<affiliation wicri:level="2"><nlm:aff id="A22">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Mayo Clinic, Rochester, MN</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hartikainen, Anna Liisa" sort="Hartikainen, Anna Liisa" uniqKey="Hartikainen A" first="Anna-Liisa" last="Hartikainen">Anna-Liisa Hartikainen</name>
<affiliation wicri:level="1"><nlm:aff id="A23">Institute of Clinical Medicine, Obstetrics and Gynecology, University of Oulu, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Institute of Clinical Medicine, Obstetrics and Gynecology, University of Oulu, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pennell, Craig E" sort="Pennell, Craig E" uniqKey="Pennell C" first="Craig E." last="Pennell">Craig E. Pennell</name>
<affiliation wicri:level="1"><nlm:aff id="A24">School of Women’s & Infant’s Health, University of Western Australia, Crawley, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Women’s & Infant’s Health, University of Western Australia, Crawley</wicri:regionArea>
<wicri:noRegion>Crawley</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Thiering, Elisabeth" sort="Thiering, Elisabeth" uniqKey="Thiering E" first="Elisabeth" last="Thiering">Elisabeth Thiering</name>
<affiliation wicri:level="1"><nlm:aff id="A25">Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Centre for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Centre for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Steegers, Eric A P" sort="Steegers, Eric A P" uniqKey="Steegers E" first="Eric A. P." last="Steegers">Eric A. P. Steegers</name>
<affiliation wicri:level="3"><nlm:aff id="A26">Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hakonarson, Hakon" sort="Hakonarson, Hakon" uniqKey="Hakonarson H" first="Hakon" last="Hakonarson">Hakon Hakonarson</name>
<affiliation wicri:level="3"><nlm:aff id="A27">Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A28">Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Heinrich, Joachim" sort="Heinrich, Joachim" uniqKey="Heinrich J" first="Joachim" last="Heinrich">Joachim Heinrich</name>
<affiliation wicri:level="1"><nlm:aff id="A24">School of Women’s & Infant’s Health, University of Western Australia, Crawley, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Women’s & Infant’s Health, University of Western Australia, Crawley</wicri:regionArea>
<wicri:noRegion>Crawley</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Palmer, Lyle J" sort="Palmer, Lyle J" uniqKey="Palmer L" first="Lyle J" last="Palmer">Lyle J. Palmer</name>
<affiliation wicri:level="4"><nlm:aff id="A29">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, University of Toronto, Toronto, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, University of Toronto, Toronto</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jarvelin, Marjo Riitta" sort="Jarvelin, Marjo Riitta" uniqKey="Jarvelin M" first="Marjo-Riitta" last="Jarvelin">Marjo-Riitta Jarvelin</name>
<affiliation wicri:level="3"><nlm:aff id="A30">Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A31">Institute of Health Sciences, University of Oulu, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Institute of Health Sciences, University of Oulu, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A32">Biocenter Oulu, Univeristy of Oulu, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Biocenter Oulu, Univeristy of Oulu, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A33">Department of Children, Young People and Families, National Institute of Health and Welfare, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Children, Young People and Families, National Institute of Health and Welfare, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I." last="Mccarthy">Mark I. Mccarthy</name>
<affiliation wicri:level="4"><nlm:aff id="A34">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford</wicri:regionArea>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A35">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford</wicri:regionArea>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
</author>
<author><name sortKey="Grant, Struan F A" sort="Grant, Struan F A" uniqKey="Grant S" first="Struan F. A." last="Grant">Struan F. A. Grant</name>
<affiliation wicri:level="3"><nlm:aff id="A27">Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A28">Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="St Pourcain, Beate" sort="St Pourcain, Beate" uniqKey="St Pourcain B" first="Beate" last="St Pourcain">Beate St Pourcain</name>
<affiliation wicri:level="1"><nlm:aff id="A36">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Timpson, Nicholas J" sort="Timpson, Nicholas J" uniqKey="Timpson N" first="Nicholas J" last="Timpson">Nicholas J. Timpson</name>
<affiliation wicri:level="1"><nlm:aff id="A36">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name>
<affiliation wicri:level="1"><nlm:aff id="A36">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sovio, Ulla" sort="Sovio, Ulla" uniqKey="Sovio U" first="Ulla" last="Sovio">Ulla Sovio</name>
<affiliation wicri:level="3"><nlm:aff id="A30">Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A37">Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nalls, Mike A" sort="Nalls, Mike A" uniqKey="Nalls M" first="Mike A." last="Nalls">Mike A. Nalls</name>
<affiliation wicri:level="2"><nlm:aff id="A39">Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Au, Rhoda" sort="Au, Rhoda" uniqKey="Au R" first="Rhoda" last="Au">Rhoda Au</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A10">Department of Neurology, Medical University Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Neurology, Medical University Graz</wicri:regionArea>
<wicri:noRegion>Medical University Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Netherlands Consortium for Healthy Aging, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium for Healthy Aging</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gudnason, Haukur" sort="Gudnason, Haukur" uniqKey="Gudnason H" first="Haukur" last="Gudnason">Haukur Gudnason</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Icelandic Heart Association, Kopavogur</wicri:regionArea>
<wicri:noRegion>Kopavogur</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Der Lugt, Aad" sort="Van Der Lugt, Aad" uniqKey="Van Der Lugt A" first="Aad" last="Van Der Lugt">Aad Van Der Lugt</name>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name>
<affiliation wicri:level="2"><nlm:aff id="A40">Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meeks, William M" sort="Meeks, William M" uniqKey="Meeks W" first="William M." last="Meeks">William M. Meeks</name>
<affiliation wicri:level="2"><nlm:aff id="A41">Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</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 wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Buchem, Mark A" sort="Van Buchem, Mark A" uniqKey="Van Buchem M" first="Mark A." last="Van Buchem">Mark A. Van Buchem</name>
<affiliation wicri:level="3"><nlm:aff id="A42">Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Leiden University Medical Center, Leiden</wicri:regionArea>
<placeName><settlement type="city">Leyde</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Catellier, Diane" sort="Catellier, Diane" uniqKey="Catellier D" first="Diane" last="Catellier">Diane Catellier</name>
<affiliation wicri:level="2"><nlm:aff id="A43">Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, University of North Carolina, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jaddoe, Vincent W V" sort="Jaddoe, Vincent W V" uniqKey="Jaddoe V" first="Vincent W. V." last="Jaddoe">Vincent W. V. Jaddoe</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A13">Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A14">The Generation R Study, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Generation R Study, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Icelandic Heart Association, Kopavogur</wicri:regionArea>
<wicri:noRegion>Kopavogur</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Faculty of Medicine, University of Iceland, Reykjavik</wicri:regionArea>
<wicri:noRegion>Reykjavik</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A41">Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wolf, Philip A" sort="Wolf, Philip A" uniqKey="Wolf P" first="Philip A." last="Wolf">Philip A. Wolf</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A9">The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</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 wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Netherlands Consortium for Healthy Aging, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium for Healthy Aging</wicri:regionArea>
</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 wicri:level="2"><nlm:aff id="A41">Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schmidt, Helena" sort="Schmidt, Helena" uniqKey="Schmidt H" first="Helena" last="Schmidt">Helena Schmidt</name>
<affiliation wicri:level="1"><nlm:aff id="A44">Institute of Molecular Biology and Biochemistry, Medical University Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Medical University Graz</wicri:regionArea>
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</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 wicri:level="2"><nlm:aff id="A40">Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Breteler, Monique M B" sort="Breteler, Monique M B" uniqKey="Breteler M" first="Monique M. B." last="Breteler">Monique M. B. Breteler</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Netherlands Consortium for Healthy Aging, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium for Healthy Aging</wicri:regionArea>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A45">German Center for Neurologic Diseases (DZNE), Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Center for Neurologic Diseases (DZNE), Bonn</wicri:regionArea>
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<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Decarli, Charles" sort="Decarli, Charles" uniqKey="Decarli C" first="Charles" last="Decarli">Charles Decarli</name>
<affiliation wicri:level="2"><nlm:aff id="A46">Department of Neurology and Center of Neuroscience, University of California at Davis, Sacramento, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology and Center of Neuroscience, University of California at Davis, Sacramento, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</titleStmt>
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<idno type="pmid">22504418</idno>
<idno type="pmc">3618290</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Common variants at 6q22 and 17q21 are associated with intracranial volume</title>
<author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M. Arfan" last="Ikram">M. Arfan Ikram</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Netherlands Consortium for Healthy Aging, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium for Healthy Aging</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name>
<affiliation wicri:level="2"><nlm:aff id="A4">Institute of Molecular Medicine and Human Genetics Center, University of Texas, Houston Health Sciences Center, Houston, TX, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Institute of Molecular Medicine and Human Genetics Center, University of Texas, Houston Health Sciences Center, Houston, TX</wicri:regionArea>
<placeName><region type="state">Texas</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Smith, Albert V" sort="Smith, Albert V" uniqKey="Smith A" first="Albert V." last="Smith">Albert V. Smith</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Icelandic Heart Association, Kopavogur</wicri:regionArea>
<wicri:noRegion>Kopavogur</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Faculty of Medicine, University of Iceland, Reykjavik</wicri:regionArea>
<wicri:noRegion>Reykjavik</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A8">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University School of Public Health, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A9">The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schmidt, Reinhold" sort="Schmidt, Reinhold" uniqKey="Schmidt R" first="Reinhold" last="Schmidt">Reinhold Schmidt</name>
<affiliation wicri:level="1"><nlm:aff id="A10">Department of Neurology, Medical University Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Neurology, Medical University Graz</wicri:regionArea>
<wicri:noRegion>Medical University Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stéphanie" last="Debette">Stéphanie Debette</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A8">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University School of Public Health, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A11">INSERM, U708, Neuroepidemiology, Paris, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM, U708, Neuroepidemiology, Paris</wicri:regionArea>
<placeName><region type="region">Île-de-France</region>
<region type="old region">Île-de-France</region>
<settlement type="city">Paris</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vrooman, Henri A" sort="Vrooman, Henri A" uniqKey="Vrooman H" first="Henri A." last="Vrooman">Henri A. Vrooman</name>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A12">Department of Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Medical Informatics, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sigurdsson, Sigurdur" sort="Sigurdsson, Sigurdur" uniqKey="Sigurdsson S" first="Sigurdur" last="Sigurdsson">Sigurdur Sigurdsson</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Icelandic Heart Association, Kopavogur</wicri:regionArea>
<wicri:noRegion>Kopavogur</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ropele, Stefan" sort="Ropele, Stefan" uniqKey="Ropele S" first="Stefan" last="Ropele">Stefan Ropele</name>
<affiliation wicri:level="1"><nlm:aff id="A10">Department of Neurology, Medical University Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Neurology, Medical University Graz</wicri:regionArea>
<wicri:noRegion>Medical University Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Taal, H Rob" sort="Taal, H Rob" uniqKey="Taal H" first="H. Rob" last="Taal">H. Rob Taal</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A13">Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A14">The Generation R Study, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Generation R Study, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Mook Kanamori, Dennis O" sort="Mook Kanamori, Dennis O" uniqKey="Mook Kanamori D" first="Dennis O." last="Mook-Kanamori">Dennis O. Mook-Kanamori</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A13">Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A14">The Generation R Study, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Generation R Study, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A15">Department of Physiology and Biophysics, Weill Cornell Medical College – Qatar, Doha, Qatar</nlm:aff>
<country xml:lang="fr">Qatar</country>
<wicri:regionArea>Department of Physiology and Biophysics, Weill Cornell Medical College – Qatar, Doha</wicri:regionArea>
<wicri:noRegion>Doha</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Coker, Laura H" sort="Coker, Laura H" uniqKey="Coker L" first="Laura H." last="Coker">Laura H. Coker</name>
<affiliation wicri:level="2"><nlm:aff id="A16">Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</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 wicri:level="4"><nlm:aff id="A17">Department of Neurology and Epidemiology, University of Washington, Seattle, WA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology and Epidemiology, University of Washington, Seattle, WA</wicri:regionArea>
<placeName><region type="state">Washington (État)</region>
<settlement type="city">Seattle</settlement>
</placeName>
<orgName type="university">Université de Washington</orgName>
</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 wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A12">Department of Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Medical Informatics, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A18">Faculty of Applied Sciences, Delft University of Technology, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Faculty of Applied Sciences, Delft University of Technology</wicri:regionArea>
<wicri:noRegion>Delft University of Technology</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Destefano, Anita L" sort="Destefano, Anita L" uniqKey="Destefano A" first="Anita L." last="Destefano">Anita L. Destefano</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A8">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University School of Public Health, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A9">The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Beiser, Alexa" sort="Beiser, Alexa" uniqKey="Beiser A" first="Alexa" last="Beiser">Alexa Beiser</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A8">Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, Boston University School of Public Health, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A9">The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zijdenbos, Alex P" sort="Zijdenbos, Alex P" uniqKey="Zijdenbos A" first="Alex P." last="Zijdenbos">Alex P. Zijdenbos</name>
<affiliation wicri:level="3"><nlm:aff id="A19">Biospective Inc, Montreal, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Biospective Inc, Montreal</wicri:regionArea>
<placeName><settlement type="city">Montréal</settlement>
<region type="state">Québec</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Struchalin, Maksim" sort="Struchalin, Maksim" uniqKey="Struchalin M" first="Maksim" last="Struchalin">Maksim Struchalin</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jack, Clifford R" sort="Jack, Clifford R" uniqKey="Jack C" first="Clifford R." last="Jack">Clifford R. Jack</name>
<affiliation wicri:level="2"><nlm:aff id="A20">Department of Radiology, Mayo Clinic, Rochester, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Mayo Clinic, Rochester, MN</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Rivadeneira, Fernando" sort="Rivadeneira, Fernando" uniqKey="Rivadeneira F" first="Fernando" last="Rivadeneira">Fernando Rivadeneira</name>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A21">Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Uitterlinden, Andre G" sort="Uitterlinden, Andre G" uniqKey="Uitterlinden A" first="Andre G." last="Uitterlinden">Andre G. Uitterlinden</name>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A21">Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Knopman, David S" sort="Knopman, David S" uniqKey="Knopman D" first="David S." last="Knopman">David S. Knopman</name>
<affiliation wicri:level="2"><nlm:aff id="A22">Department of Neurology, Mayo Clinic, Rochester, MN, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Mayo Clinic, Rochester, MN</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hartikainen, Anna Liisa" sort="Hartikainen, Anna Liisa" uniqKey="Hartikainen A" first="Anna-Liisa" last="Hartikainen">Anna-Liisa Hartikainen</name>
<affiliation wicri:level="1"><nlm:aff id="A23">Institute of Clinical Medicine, Obstetrics and Gynecology, University of Oulu, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Institute of Clinical Medicine, Obstetrics and Gynecology, University of Oulu, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Pennell, Craig E" sort="Pennell, Craig E" uniqKey="Pennell C" first="Craig E." last="Pennell">Craig E. Pennell</name>
<affiliation wicri:level="1"><nlm:aff id="A24">School of Women’s & Infant’s Health, University of Western Australia, Crawley, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Women’s & Infant’s Health, University of Western Australia, Crawley</wicri:regionArea>
<wicri:noRegion>Crawley</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Thiering, Elisabeth" sort="Thiering, Elisabeth" uniqKey="Thiering E" first="Elisabeth" last="Thiering">Elisabeth Thiering</name>
<affiliation wicri:level="1"><nlm:aff id="A25">Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Centre for Environmental Health, Neuherberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Centre for Environmental Health, Neuherberg</wicri:regionArea>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
<wicri:noRegion>Neuherberg</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Steegers, Eric A P" sort="Steegers, Eric A P" uniqKey="Steegers E" first="Eric A. P." last="Steegers">Eric A. P. Steegers</name>
<affiliation wicri:level="3"><nlm:aff id="A26">Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Hakonarson, Hakon" sort="Hakonarson, Hakon" uniqKey="Hakonarson H" first="Hakon" last="Hakonarson">Hakon Hakonarson</name>
<affiliation wicri:level="3"><nlm:aff id="A27">Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A28">Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Heinrich, Joachim" sort="Heinrich, Joachim" uniqKey="Heinrich J" first="Joachim" last="Heinrich">Joachim Heinrich</name>
<affiliation wicri:level="1"><nlm:aff id="A24">School of Women’s & Infant’s Health, University of Western Australia, Crawley, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>School of Women’s & Infant’s Health, University of Western Australia, Crawley</wicri:regionArea>
<wicri:noRegion>Crawley</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Palmer, Lyle J" sort="Palmer, Lyle J" uniqKey="Palmer L" first="Lyle J" last="Palmer">Lyle J. Palmer</name>
<affiliation wicri:level="4"><nlm:aff id="A29">Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, University of Toronto, Toronto, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, University of Toronto, Toronto</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jarvelin, Marjo Riitta" sort="Jarvelin, Marjo Riitta" uniqKey="Jarvelin M" first="Marjo-Riitta" last="Jarvelin">Marjo-Riitta Jarvelin</name>
<affiliation wicri:level="3"><nlm:aff id="A30">Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A31">Institute of Health Sciences, University of Oulu, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Institute of Health Sciences, University of Oulu, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A32">Biocenter Oulu, Univeristy of Oulu, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Biocenter Oulu, Univeristy of Oulu, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A33">Department of Children, Young People and Families, National Institute of Health and Welfare, Oulu, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Department of Children, Young People and Families, National Institute of Health and Welfare, Oulu</wicri:regionArea>
<wicri:noRegion>Oulu</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Mccarthy, Mark I" sort="Mccarthy, Mark I" uniqKey="Mccarthy M" first="Mark I." last="Mccarthy">Mark I. Mccarthy</name>
<affiliation wicri:level="4"><nlm:aff id="A34">Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford</wicri:regionArea>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
<affiliation wicri:level="4"><nlm:aff id="A35">Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford</wicri:regionArea>
<placeName><settlement type="city">Oxford</settlement>
<region type="country">Angleterre</region>
<region type="comté" nuts="2">Oxfordshire</region>
<settlement type="city">Oxford</settlement>
</placeName>
<orgName type="university">Université d'Oxford</orgName>
</affiliation>
</author>
<author><name sortKey="Grant, Struan F A" sort="Grant, Struan F A" uniqKey="Grant S" first="Struan F. A." last="Grant">Struan F. A. Grant</name>
<affiliation wicri:level="3"><nlm:aff id="A27">Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A28">Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia</wicri:regionArea>
<placeName><settlement type="city">Philadelphie</settlement>
<region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="St Pourcain, Beate" sort="St Pourcain, Beate" uniqKey="St Pourcain B" first="Beate" last="St Pourcain">Beate St Pourcain</name>
<affiliation wicri:level="1"><nlm:aff id="A36">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Timpson, Nicholas J" sort="Timpson, Nicholas J" uniqKey="Timpson N" first="Nicholas J" last="Timpson">Nicholas J. Timpson</name>
<affiliation wicri:level="1"><nlm:aff id="A36">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Smith, George Davey" sort="Smith, George Davey" uniqKey="Smith G" first="George Davey" last="Smith">George Davey Smith</name>
<affiliation wicri:level="1"><nlm:aff id="A36">MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol</wicri:regionArea>
<wicri:noRegion>Bristol</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sovio, Ulla" sort="Sovio, Ulla" uniqKey="Sovio U" first="Ulla" last="Sovio">Ulla Sovio</name>
<affiliation wicri:level="3"><nlm:aff id="A30">Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A37">Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London</wicri:regionArea>
<placeName><settlement type="city">Londres</settlement>
<region type="country">Angleterre</region>
<region type="région" nuts="1">Grand Londres</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Nalls, Mike A" sort="Nalls, Mike A" uniqKey="Nalls M" first="Mike A." last="Nalls">Mike A. Nalls</name>
<affiliation wicri:level="2"><nlm:aff id="A39">Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Au, Rhoda" sort="Au, Rhoda" uniqKey="Au R" first="Rhoda" last="Au">Rhoda Au</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A10">Department of Neurology, Medical University Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Neurology, Medical University Graz</wicri:regionArea>
<wicri:noRegion>Medical University Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Netherlands Consortium for Healthy Aging, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium for Healthy Aging</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Gudnason, Haukur" sort="Gudnason, Haukur" uniqKey="Gudnason H" first="Haukur" last="Gudnason">Haukur Gudnason</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Icelandic Heart Association, Kopavogur</wicri:regionArea>
<wicri:noRegion>Kopavogur</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Der Lugt, Aad" sort="Van Der Lugt, Aad" uniqKey="Van Der Lugt A" first="Aad" last="Van Der Lugt">Aad Van Der Lugt</name>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Harris, Tamara B" sort="Harris, Tamara B" uniqKey="Harris T" first="Tamara B." last="Harris">Tamara B. Harris</name>
<affiliation wicri:level="2"><nlm:aff id="A40">Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Meeks, William M" sort="Meeks, William M" uniqKey="Meeks W" first="William M." last="Meeks">William M. Meeks</name>
<affiliation wicri:level="2"><nlm:aff id="A41">Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</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 wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A2">Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Van Buchem, Mark A" sort="Van Buchem, Mark A" uniqKey="Van Buchem M" first="Mark A." last="Van Buchem">Mark A. Van Buchem</name>
<affiliation wicri:level="3"><nlm:aff id="A42">Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Leiden University Medical Center, Leiden</wicri:regionArea>
<placeName><settlement type="city">Leyde</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Catellier, Diane" sort="Catellier, Diane" uniqKey="Catellier D" first="Diane" last="Catellier">Diane Catellier</name>
<affiliation wicri:level="2"><nlm:aff id="A43">Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Biostatistics, University of North Carolina, Chapel Hill, NC</wicri:regionArea>
<placeName><region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Jaddoe, Vincent W V" sort="Jaddoe, Vincent W V" uniqKey="Jaddoe V" first="Vincent W. V." last="Jaddoe">Vincent W. V. Jaddoe</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A13">Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A14">The Generation R Study, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>The Generation R Study, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Gudnason, Vilmundur" sort="Gudnason, Vilmundur" uniqKey="Gudnason V" first="Vilmundur" last="Gudnason">Vilmundur Gudnason</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Icelandic Heart Association, Kopavogur, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Icelandic Heart Association, Kopavogur</wicri:regionArea>
<wicri:noRegion>Kopavogur</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Faculty of Medicine, University of Iceland, Reykjavik, Iceland</nlm:aff>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Faculty of Medicine, University of Iceland, Reykjavik</wicri:regionArea>
<wicri:noRegion>Reykjavik</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A41">Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Wolf, Philip A" sort="Wolf, Philip A" uniqKey="Wolf P" first="Philip A." last="Wolf">Philip A. Wolf</name>
<affiliation wicri:level="2"><nlm:aff id="A7">Department of Neurology, Boston University School of Medicine, Boston, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="A9">The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</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 wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Netherlands Consortium for Healthy Aging, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium for Healthy Aging</wicri:regionArea>
</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 wicri:level="2"><nlm:aff id="A41">Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Schmidt, Helena" sort="Schmidt, Helena" uniqKey="Schmidt H" first="Helena" last="Schmidt">Helena Schmidt</name>
<affiliation wicri:level="1"><nlm:aff id="A44">Institute of Molecular Biology and Biochemistry, Medical University Graz, Austria</nlm:aff>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Medical University Graz</wicri:regionArea>
<wicri:noRegion>Medical University Graz</wicri:noRegion>
</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 wicri:level="2"><nlm:aff id="A40">Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Breteler, Monique M B" sort="Breteler, Monique M B" uniqKey="Breteler M" first="Monique M. B." last="Breteler">Monique M. B. Breteler</name>
<affiliation wicri:level="3"><nlm:aff id="A1">Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A3">Netherlands Consortium for Healthy Aging, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Netherlands Consortium for Healthy Aging</wicri:regionArea>
</affiliation>
<affiliation wicri:level="3"><nlm:aff id="A45">German Center for Neurologic Diseases (DZNE), Bonn, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>German Center for Neurologic Diseases (DZNE), Bonn</wicri:regionArea>
<placeName><region type="land" nuts="1">Rhénanie-du-Nord-Westphalie</region>
<region type="district" nuts="2">District de Cologne</region>
<settlement type="city">Bonn</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Decarli, Charles" sort="Decarli, Charles" uniqKey="Decarli C" first="Charles" last="Decarli">Charles Decarli</name>
<affiliation wicri:level="2"><nlm:aff id="A46">Department of Neurology and Center of Neuroscience, University of California at Davis, Sacramento, CA, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology and Center of Neuroscience, University of California at Davis, Sacramento, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Nature genetics</title>
<idno type="ISSN">1061-4036</idno>
<idno type="eISSN">1546-1718</idno>
<imprint><date when="2012">2012</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass></textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P3">During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study in 8,175 community-dwelling elderly did not reveal any genome-wide significant associations (p<5*10<sup>−8</sup>
) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (p=3.4*10<sup>−11</sup>
), a known height locus on chromosome 6q22, and rs9915547, tagging the inversion on chromosome 17q21 (p=1.5*10<sup>−12</sup>
). We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 older persons (p=1.1*10<sup>−3</sup>
for 6q22 and p=1.2*10<sup>−3</sup>
for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age 14.5 months). Our data identify two loci associated with head size, with the inversion on 17q21 also likely involved in attaining maximal brain size.</p>
</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">9216904</journal-id>
<journal-id journal-id-type="pubmed-jr-id">2419</journal-id>
<journal-id journal-id-type="nlm-ta">Nat Genet</journal-id>
<journal-id journal-id-type="iso-abbrev">Nat. Genet.</journal-id>
<journal-title-group><journal-title>Nature genetics</journal-title>
</journal-title-group>
<issn pub-type="ppub">1061-4036</issn>
<issn pub-type="epub">1546-1718</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">22504418</article-id>
<article-id pub-id-type="pmc">3618290</article-id>
<article-id pub-id-type="doi">10.1038/ng.2245</article-id>
<article-id pub-id-type="manuscript">NIHMS428966</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Common variants at 6q22 and 17q21 are associated with intracranial volume</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Ikram</surname>
<given-names>M. Arfan</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="corresp" rid="cor1">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Fornage</surname>
<given-names>Myriam</given-names>
</name>
<xref ref-type="aff" rid="A4">4</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Smith</surname>
<given-names>Albert V.</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
<xref ref-type="aff" rid="A6">6</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Seshadri</surname>
<given-names>Sudha</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schmidt</surname>
<given-names>Reinhold</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
<xref ref-type="author-notes" rid="FN1">*</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Debette</surname>
<given-names>Stéphanie</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A11">11</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vrooman</surname>
<given-names>Henri A.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A12">12</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sigurdsson</surname>
<given-names>Sigurdur</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Ropele</surname>
<given-names>Stefan</given-names>
</name>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Taal</surname>
<given-names>H. Rob</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mook-Kanamori</surname>
<given-names>Dennis O.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
<xref ref-type="aff" rid="A15">15</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Coker</surname>
<given-names>Laura H.</given-names>
</name>
<xref ref-type="aff" rid="A16">16</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Longstreth</surname>
<given-names>W.T.</given-names>
<suffix>Jr.</suffix>
</name>
<xref ref-type="aff" rid="A17">17</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Niessen</surname>
<given-names>Wiro J.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A12">12</xref>
<xref ref-type="aff" rid="A18">18</xref>
</contrib>
<contrib contrib-type="author"><name><surname>DeStefano</surname>
<given-names>Anita L.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Beiser</surname>
<given-names>Alexa</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A8">8</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Zijdenbos</surname>
<given-names>Alex P.</given-names>
</name>
<xref ref-type="aff" rid="A19">19</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Struchalin</surname>
<given-names>Maksim</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jack</surname>
<given-names>Clifford R.</given-names>
<suffix>Jr.</suffix>
</name>
<xref ref-type="aff" rid="A20">20</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Rivadeneira</surname>
<given-names>Fernando</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Uitterlinden</surname>
<given-names>Andre G.</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
<xref ref-type="aff" rid="A21">21</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Knopman</surname>
<given-names>David S.</given-names>
</name>
<xref ref-type="aff" rid="A22">22</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hartikainen</surname>
<given-names>Anna-Liisa</given-names>
</name>
<xref ref-type="aff" rid="A23">23</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Pennell</surname>
<given-names>Craig E.</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Thiering</surname>
<given-names>Elisabeth</given-names>
</name>
<xref ref-type="aff" rid="A25">25</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Steegers</surname>
<given-names>Eric A.P.</given-names>
</name>
<xref ref-type="aff" rid="A26">26</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hakonarson</surname>
<given-names>Hakon</given-names>
</name>
<xref ref-type="aff" rid="A27">27</xref>
<xref ref-type="aff" rid="A28">28</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Heinrich</surname>
<given-names>Joachim</given-names>
</name>
<xref ref-type="aff" rid="A24">24</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Palmer</surname>
<given-names>Lyle J</given-names>
</name>
<xref ref-type="aff" rid="A29">29</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jarvelin</surname>
<given-names>Marjo-Riitta</given-names>
</name>
<xref ref-type="aff" rid="A30">30</xref>
<xref ref-type="aff" rid="A31">31</xref>
<xref ref-type="aff" rid="A32">32</xref>
<xref ref-type="aff" rid="A33">33</xref>
</contrib>
<contrib contrib-type="author"><name><surname>McCarthy</surname>
<given-names>Mark I.</given-names>
</name>
<xref ref-type="aff" rid="A34">34</xref>
<xref ref-type="aff" rid="A35">35</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Grant</surname>
<given-names>Struan F.A.</given-names>
</name>
<xref ref-type="aff" rid="A27">27</xref>
<xref ref-type="aff" rid="A28">28</xref>
</contrib>
<contrib contrib-type="author"><name><surname>St Pourcain</surname>
<given-names>Beate</given-names>
</name>
<xref ref-type="aff" rid="A36">36</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Timpson</surname>
<given-names>Nicholas J</given-names>
</name>
<xref ref-type="aff" rid="A36">36</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Smith</surname>
<given-names>George Davey</given-names>
</name>
<xref ref-type="aff" rid="A36">36</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Sovio</surname>
<given-names>Ulla</given-names>
</name>
<xref ref-type="aff" rid="A30">30</xref>
<xref ref-type="aff" rid="A37">37</xref>
</contrib>
<contrib contrib-type="author"><collab>the EGG consortium</collab>
<xref ref-type="author-notes" rid="FN2">38</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Nalls</surname>
<given-names>Mike A.</given-names>
</name>
<xref ref-type="aff" rid="A39">39</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Au</surname>
<given-names>Rhoda</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A10">10</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Hofman</surname>
<given-names>Albert</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gudnason</surname>
<given-names>Haukur</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van der Lugt</surname>
<given-names>Aad</given-names>
</name>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Harris</surname>
<given-names>Tamara B.</given-names>
</name>
<xref ref-type="aff" rid="A40">40</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Meeks</surname>
<given-names>William M.</given-names>
</name>
<xref ref-type="aff" rid="A41">41</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Vernooij</surname>
<given-names>Meike W.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Buchem</surname>
<given-names>Mark A.</given-names>
</name>
<xref ref-type="aff" rid="A42">42</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Catellier</surname>
<given-names>Diane</given-names>
</name>
<xref ref-type="aff" rid="A43">43</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Jaddoe</surname>
<given-names>Vincent W.V.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A13">13</xref>
<xref ref-type="aff" rid="A14">14</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Gudnason</surname>
<given-names>Vilmundur</given-names>
</name>
<xref ref-type="aff" rid="A5">5</xref>
<xref ref-type="aff" rid="A6">6</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Windham</surname>
<given-names>B. Gwen</given-names>
</name>
<xref ref-type="aff" rid="A41">41</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Wolf</surname>
<given-names>Philip A.</given-names>
</name>
<xref ref-type="aff" rid="A7">7</xref>
<xref ref-type="aff" rid="A9">9</xref>
</contrib>
<contrib contrib-type="author"><name><surname>van Duijn</surname>
<given-names>Cornelia M.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Mosley</surname>
<given-names>Thomas H.</given-names>
<suffix>Jr.</suffix>
</name>
<xref ref-type="aff" rid="A41">41</xref>
<xref ref-type="author-notes" rid="FN1">**</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Schmidt</surname>
<given-names>Helena</given-names>
</name>
<xref ref-type="aff" rid="A44">44</xref>
<xref ref-type="author-notes" rid="FN1">**</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Launer</surname>
<given-names>Lenore J.</given-names>
</name>
<xref ref-type="aff" rid="A40">40</xref>
<xref ref-type="author-notes" rid="FN1">**</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Breteler</surname>
<given-names>Monique M.B.</given-names>
</name>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="aff" rid="A3">3</xref>
<xref ref-type="aff" rid="A45">45</xref>
<xref ref-type="author-notes" rid="FN1">**</xref>
</contrib>
<contrib contrib-type="author"><name><surname>DeCarli</surname>
<given-names>Charles</given-names>
</name>
<on-behalf-of>for the CHARGE consortium</on-behalf-of>
<xref ref-type="aff" rid="A46">46</xref>
<xref ref-type="author-notes" rid="FN1">**</xref>
<xref ref-type="corresp" rid="cor1">†</xref>
</contrib>
</contrib-group>
<aff id="A1"><label>1</label>
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A2"><label>2</label>
Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A3"><label>3</label>
Netherlands Consortium for Healthy Aging, The Netherlands</aff>
<aff id="A4"><label>4</label>
Institute of Molecular Medicine and Human Genetics Center, University of Texas, Houston Health Sciences Center, Houston, TX, USA</aff>
<aff id="A5"><label>5</label>
Icelandic Heart Association, Kopavogur, Iceland</aff>
<aff id="A6"><label>6</label>
Faculty of Medicine, University of Iceland, Reykjavik, Iceland</aff>
<aff id="A7"><label>7</label>
Department of Neurology, Boston University School of Medicine, Boston, MA, USA</aff>
<aff id="A8"><label>8</label>
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA</aff>
<aff id="A9"><label>9</label>
The National Heart Lung and Blood Institute’s Framingham Heart Study, Framingham, MA, USA</aff>
<aff id="A10"><label>10</label>
Department of Neurology, Medical University Graz, Austria</aff>
<aff id="A11"><label>11</label>
INSERM, U708, Neuroepidemiology, Paris, France</aff>
<aff id="A12"><label>12</label>
Department of Medical Informatics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A13"><label>13</label>
Department of Pediatrics, Erasmus MC University Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A14"><label>14</label>
The Generation R Study, Erasmus MC University Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A15"><label>15</label>
Department of Physiology and Biophysics, Weill Cornell Medical College – Qatar, Doha, Qatar</aff>
<aff id="A16"><label>16</label>
Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA</aff>
<aff id="A17"><label>17</label>
Department of Neurology and Epidemiology, University of Washington, Seattle, WA, USA</aff>
<aff id="A18"><label>18</label>
Faculty of Applied Sciences, Delft University of Technology, The Netherlands</aff>
<aff id="A19"><label>19</label>
Biospective Inc, Montreal, Canada</aff>
<aff id="A20"><label>20</label>
Department of Radiology, Mayo Clinic, Rochester, MN, USA</aff>
<aff id="A21"><label>21</label>
Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A22"><label>22</label>
Department of Neurology, Mayo Clinic, Rochester, MN, USA</aff>
<aff id="A23"><label>23</label>
Institute of Clinical Medicine, Obstetrics and Gynecology, University of Oulu, Oulu, Finland</aff>
<aff id="A24"><label>24</label>
School of Women’s & Infant’s Health, University of Western Australia, Crawley, Australia</aff>
<aff id="A25"><label>25</label>
Institute of Epidemiology I, Helmholtz Zentrum Munchen - German Research Centre for Environmental Health, Neuherberg, Germany</aff>
<aff id="A26"><label>26</label>
Department of Obstetrics and Gynaecology, Erasmus MC University Medical Center, Rotterdam, The Netherlands</aff>
<aff id="A27"><label>27</label>
Center for Applied Genomics, Abramsom Research Center, The Children’s Hospital of Philadelphia, Philadelphia, USA</aff>
<aff id="A28"><label>28</label>
Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Philadelphia, USA</aff>
<aff id="A29"><label>29</label>
Genetic Epidemiology and Biostatistics Platform, Ontario Institute for Cancer Research, University of Toronto, Toronto, Canada</aff>
<aff id="A30"><label>30</label>
Department of Epidemiology and Biostatistics, School of Public Health, MRC-HPA Centre for Environmental and Health, Faculty of Medicine, Imperial College, London, UK</aff>
<aff id="A31"><label>31</label>
Institute of Health Sciences, University of Oulu, Oulu, Finland</aff>
<aff id="A32"><label>32</label>
Biocenter Oulu, Univeristy of Oulu, Oulu, Finland</aff>
<aff id="A33"><label>33</label>
Department of Children, Young People and Families, National Institute of Health and Welfare, Oulu, Finland</aff>
<aff id="A34"><label>34</label>
Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK</aff>
<aff id="A35"><label>35</label>
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK</aff>
<aff id="A36"><label>36</label>
MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK</aff>
<aff id="A37"><label>37</label>
Department of Medical Statistics, London School of Hygiene and Tropical Medicine, London, UK</aff>
<aff id="A39"><label>39</label>
Laboratory of Neurogenetics, National Institute on Aging, National Institute of Health, Bethesda, MD, USA</aff>
<aff id="A40"><label>40</label>
Laboratory of Epidemiology, Demography, and Biometry, National Institute of Health, Bethesda, MD, USA</aff>
<aff id="A41"><label>41</label>
Department of Medicine (Geriatrics) and Neurology, University of Mississippi Medical Center, Jackson, MS, USA</aff>
<aff id="A42"><label>42</label>
Department of Radiology, Leiden University Medical Center, Leiden, The Netherlands</aff>
<aff id="A43"><label>43</label>
Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA</aff>
<aff id="A44"><label>44</label>
Institute of Molecular Biology and Biochemistry, Medical University Graz, Austria</aff>
<aff id="A45"><label>45</label>
German Center for Neurologic Diseases (DZNE), Bonn, Germany</aff>
<aff id="A46"><label>46</label>
Department of Neurology and Center of Neuroscience, University of California at Davis, Sacramento, CA, USA</aff>
<author-notes><corresp id="cor1"><label>†</label>
<bold>Correspondence to:</bold>
M.A. Ikram, Department of Epidemiology, Erasmus MC University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands. Phone: + 31107043930 Fax: + 31107044657 <email>m.a.ikram@erasmusmc.nl</email>
or C. DeCarli, Department of Neurology and Center of Neuroscience, University of California at Davis, 4860 Y Street, Suite 3700, Sacramento, CA 95817, USA. <email>cdecarli@ucdavis.edu</email>
</corresp>
<fn id="FN1" fn-type="equal"><p id="P1">All starred first * and last ** authors contributed equally</p>
</fn>
<fn id="FN2"><label>38</label>
<p id="P2">A full list of contributors not mentioned here is given at the end of the manuscript</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>26</day>
<month>12</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="epub"><day>15</day>
<month>4</month>
<year>2012</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>01</day>
<month>5</month>
<year>2013</year>
</pub-date>
<volume>44</volume>
<issue>5</issue>
<fpage>539</fpage>
<lpage>544</lpage>
<abstract><p id="P3">During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study in 8,175 community-dwelling elderly did not reveal any genome-wide significant associations (p<5*10<sup>−8</sup>
) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (p=3.4*10<sup>−11</sup>
), a known height locus on chromosome 6q22, and rs9915547, tagging the inversion on chromosome 17q21 (p=1.5*10<sup>−12</sup>
). We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 older persons (p=1.1*10<sup>−3</sup>
for 6q22 and p=1.2*10<sup>−3</sup>
for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age 14.5 months). Our data identify two loci associated with head size, with the inversion on 17q21 also likely involved in attaining maximal brain size.</p>
</abstract>
<funding-group><award-group><funding-source country="United States">National Institute on Aging : NIA</funding-source>
<award-id>N01 AG012100 || AG</award-id>
</award-group>
</funding-group>
</article-meta>
</front>
</pmc>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Autriche</li>
<li>Canada</li>
<li>Finlande</li>
<li>France</li>
<li>Islande</li>
<li>Pays-Bas</li>
<li>Qatar</li>
<li>Royaume-Uni</li>
<li>États-Unis</li>
</country>
<region><li>Angleterre</li>
<li>Californie</li>
<li>Caroline du Nord</li>
<li>District de Cologne</li>
<li>Grand Londres</li>
<li>Hollande-Méridionale</li>
<li>Maryland</li>
<li>Massachusetts</li>
<li>Minnesota</li>
<li>Ontario</li>
<li>Oxfordshire</li>
<li>Pennsylvanie</li>
<li>Québec</li>
<li>Rhénanie-du-Nord-Westphalie</li>
<li>Texas</li>
<li>Washington (État)</li>
<li>État du Mississippi</li>
<li>Île-de-France</li>
</region>
<settlement><li>Bonn</li>
<li>Leyde</li>
<li>Londres</li>
<li>Montréal</li>
<li>Oxford</li>
<li>Paris</li>
<li>Philadelphie</li>
<li>Rotterdam</li>
<li>Seattle</li>
<li>Toronto</li>
</settlement>
<orgName><li>Université d'Oxford</li>
<li>Université de Toronto</li>
<li>Université de Washington</li>
</orgName>
</list>
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<name sortKey="Jaddoe, Vincent W V" sort="Jaddoe, Vincent W V" uniqKey="Jaddoe V" first="Vincent W. V." last="Jaddoe">Vincent W. V. Jaddoe</name>
<name sortKey="Mook Kanamori, Dennis O" sort="Mook Kanamori, Dennis O" uniqKey="Mook Kanamori D" first="Dennis O." last="Mook-Kanamori">Dennis O. Mook-Kanamori</name>
<name sortKey="Mook Kanamori, Dennis O" sort="Mook Kanamori, Dennis O" uniqKey="Mook Kanamori D" first="Dennis O." last="Mook-Kanamori">Dennis O. Mook-Kanamori</name>
<name sortKey="Mook Kanamori, Dennis O" sort="Mook Kanamori, Dennis O" uniqKey="Mook Kanamori D" first="Dennis O." last="Mook-Kanamori">Dennis O. Mook-Kanamori</name>
<name sortKey="Niessen, Wiro J" sort="Niessen, Wiro J" uniqKey="Niessen W" first="Wiro J." last="Niessen">Wiro J. Niessen</name>
<name sortKey="Niessen, Wiro J" sort="Niessen, Wiro J" uniqKey="Niessen W" first="Wiro J." last="Niessen">Wiro J. Niessen</name>
<name sortKey="Niessen, Wiro J" sort="Niessen, Wiro J" uniqKey="Niessen W" first="Wiro J." last="Niessen">Wiro J. Niessen</name>
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