Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.
Identifieur interne : 002F15 ( PubMed/Checkpoint ); précédent : 002F14; suivant : 002F16Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.
Auteurs : Ganesh Chauhan [France] ; Hieab H H. Adams [Pays-Bas] ; Joshua C. Bis [États-Unis] ; Galit Weinstein [États-Unis] ; Lei Yu [États-Unis] ; Anna Maria Töglhofer [Autriche] ; Albert Vernon Smith [Islande] ; Sven J. Van Der Lee [Pays-Bas] ; Rebecca F. Gottesman [États-Unis] ; Russell Thomson [Australie] ; Jing Wang [États-Unis] ; Qiong Yang [États-Unis] ; Wiro J. Niessen [Pays-Bas] ; Oscar L. Lopez [États-Unis] ; James T. Becker [États-Unis] ; Thanh G. Phan [Australie] ; Richard J. Beare [Australie] ; Konstantinos Arfanakis [États-Unis] ; Debra Fleischman [États-Unis] ; Meike W. Vernooij [Pays-Bas] ; Bernard Mazoyer [France] ; Helena Schmidt [Autriche] ; Velandai Srikanth [Australie] ; David S. Knopman [États-Unis] ; Clifford R. Jack [États-Unis] ; Philippe Amouyel [France] ; Albert Hofman [Pays-Bas] ; Charles Decarli [États-Unis] ; Christophe Tzourio [France] ; Cornelia M. Van Duijn [Pays-Bas] ; David A. Bennett [États-Unis] ; Reinhold Schmidt [Autriche] ; William T. Longstreth [États-Unis] ; Thomas H. Mosley [États-Unis] ; Myriam Fornage [États-Unis] ; Lenore J. Launer [États-Unis] ; Sudha Seshadri [États-Unis] ; M Arfan Ikram [Pays-Bas] ; Stephanie Debette [France]Source :
- Neurobiology of aging [ 1558-1497 ] ; 2015.
Descripteurs français
- KwdFr :
- Allèles, Apolipoprotéines E (génétique), Encéphale (anatomopathologie), Femelle, Hippocampe (anatomopathologie), Humains, Imagerie par résonance magnétique, Lectine-3 de type Ig liant l'acide sialique (génétique), Maladie d'Alzheimer (anatomopathologie), Maladie d'Alzheimer (génétique), Mâle, Polymorphisme de nucléotide simple, Risque, Taille d'organe (génétique), Vieillissement (anatomopathologie), Vieillissement (génétique), Étude d'association pangénomique.
- MESH :
- anatomopathologie : Encéphale, Hippocampe, Maladie d'Alzheimer, Vieillissement.
- génétique : Apolipoprotéines E, Lectine-3 de type Ig liant l'acide sialique, Maladie d'Alzheimer, Taille d'organe, Vieillissement.
- Allèles, Femelle, Humains, Imagerie par résonance magnétique, Mâle, Polymorphisme de nucléotide simple, Risque, Étude d'association pangénomique.
English descriptors
- KwdEn :
- Aging (genetics), Aging (pathology), Alleles, Alzheimer Disease (genetics), Alzheimer Disease (pathology), Apolipoproteins E (genetics), Brain (pathology), Female, Genome-Wide Association Study, Hippocampus (pathology), Humans, Magnetic Resonance Imaging, Male, Organ Size (genetics), Polymorphism, Single Nucleotide, Risk, Sialic Acid Binding Ig-like Lectin 3 (genetics).
- MESH :
- chemical , genetics : Apolipoproteins E, Sialic Acid Binding Ig-like Lectin 3.
- genetics : Aging, Alzheimer Disease, Organ Size.
- pathology : Aging, Alzheimer Disease, Brain, Hippocampus.
- Alleles, Female, Genome-Wide Association Study, Humans, Magnetic Resonance Imaging, Male, Polymorphism, Single Nucleotide, Risk.
Abstract
Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.
DOI: 10.1016/j.neurobiolaging.2014.12.028
PubMed: 25670335
Affiliations:
- Australie, Autriche, France, Islande, Pays-Bas, États-Unis
- Aquitaine, Californie, Hauts-de-France, Hollande-Méridionale, Illinois, Maryland, Massachusetts, Minnesota, Nord-Pas-de-Calais, Nouvelle-Aquitaine, Pennsylvanie, Texas, Washington (État), État du Mississippi
- Baltimore, Bordeaux, Houston, Leyde, Lille, Rotterdam, Seattle
- Université Lille 2, Université de Bordeaux, Université de Washington
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pubmed:25670335Le document en format XML
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<author><name sortKey="Weinstein, Galit" sort="Weinstein, Galit" uniqKey="Weinstein G" first="Galit" last="Weinstein">Galit Weinstein</name>
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<author><name sortKey="Yu, Lei" sort="Yu, Lei" uniqKey="Yu L" first="Lei" last="Yu">Lei Yu</name>
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<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Developmental Imaging Group, Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria</wicri:regionArea>
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<author><name sortKey="Arfanakis, Konstantinos" sort="Arfanakis, Konstantinos" uniqKey="Arfanakis K" first="Konstantinos" last="Arfanakis">Konstantinos Arfanakis</name>
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<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL</wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fleischman, Debra" sort="Fleischman, Debra" uniqKey="Fleischman D" first="Debra" last="Fleischman">Debra Fleischman</name>
<affiliation wicri:level="2"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL</wicri:regionArea>
<placeName><region type="state">Illinois</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:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam</wicri:regionArea>
<placeName><settlement type="city">Rotterdam</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
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<author><name sortKey="Mazoyer, Bernard" sort="Mazoyer, Bernard" uniqKey="Mazoyer B" first="Bernard" last="Mazoyer">Bernard Mazoyer</name>
<affiliation wicri:level="4"><nlm:affiliation>Groupe d'Imagerie Neurofonctionnelle, UMR5296, CNRS, CEA, Université de Bordeaux, Bordeaux, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Groupe d'Imagerie Neurofonctionnelle, UMR5296, CNRS, CEA, Université de Bordeaux, Bordeaux</wicri:regionArea>
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</placeName>
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<author><name sortKey="Schmidt, Helena" sort="Schmidt, Helena" uniqKey="Schmidt H" first="Helena" last="Schmidt">Helena Schmidt</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz</wicri:regionArea>
<wicri:noRegion>Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Srikanth, Velandai" sort="Srikanth, Velandai" uniqKey="Srikanth V" first="Velandai" last="Srikanth">Velandai Srikanth</name>
<affiliation wicri:level="1"><nlm:affiliation>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania</wicri:regionArea>
<wicri:noRegion>Tasmania</wicri:noRegion>
</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:affiliation>Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN</wicri:regionArea>
<placeName><region type="state">Minnesota</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:affiliation>Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France; INSERM, U744, Lille, France; Université Lille 2, Lille, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France; INSERM, U744, Lille, France; Université Lille 2, Lille</wicri:regionArea>
<placeName><region type="region">Hauts-de-France</region>
<region type="old region">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
<settlement type="city">Lille</settlement>
</placeName>
<orgName type="university">Université Lille 2</orgName>
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<author><name sortKey="Hofman, Albert" sort="Hofman, Albert" uniqKey="Hofman A" first="Albert" last="Hofman">Albert Hofman</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus 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="Decarli, Charles" sort="Decarli, Charles" uniqKey="Decarli C" first="Charles" last="Decarli">Charles Decarli</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, University of California at Davis, Davis, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of California at Davis, Davis, CA</wicri:regionArea>
<placeName><region type="state">Californie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Tzourio, Christophe" sort="Tzourio, Christophe" uniqKey="Tzourio C" first="Christophe" last="Tzourio">Christophe Tzourio</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM U897, University of Bordeaux, Bordeaux, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U897, University of Bordeaux, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</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:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden, the Netherlands; Center for Medical Systems Biology, Leiden, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden, the Netherlands; Center for Medical Systems Biology, Leiden</wicri:regionArea>
<placeName><settlement type="city">Leyde</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A" last="Bennett">David A. Bennett</name>
<affiliation wicri:level="2"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL</wicri:regionArea>
<placeName><region type="state">Illinois</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:affiliation>Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz</wicri:regionArea>
<wicri:noRegion>Medical University of Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Longstreth, William T" sort="Longstreth, William T" uniqKey="Longstreth W" first="William T" last="Longstreth">William T. Longstreth</name>
<affiliation wicri:level="4"><nlm:affiliation>Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments 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="Mosley, Thomas H" sort="Mosley, Thomas H" uniqKey="Mosley T" first="Thomas H" last="Mosley">Thomas H. Mosley</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Medicine-Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson, MS, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine-Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name>
<affiliation wicri:level="3"><nlm:affiliation>The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston</wicri:regionArea>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
</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:affiliation>Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</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:affiliation>Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden</wicri:regionArea>
<placeName><settlement type="city">Leyde</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stephanie" last="Debette">Stephanie Debette</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux, France; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Bordeaux University Hospital, Bordeaux, France. Electronic address: sdebette@bu.edu.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux, France; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Bordeaux University Hospital, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PubMed</idno>
<date when="2015">2015</date>
<idno type="RBID">pubmed:25670335</idno>
<idno type="pmid">25670335</idno>
<idno type="doi">10.1016/j.neurobiolaging.2014.12.028</idno>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.</title>
<author><name sortKey="Chauhan, Ganesh" sort="Chauhan, Ganesh" uniqKey="Chauhan G" first="Ganesh" last="Chauhan">Ganesh Chauhan</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Adams, Hieab H H" sort="Adams, Hieab H H" uniqKey="Adams H" first="Hieab H H" last="Adams">Hieab H H. Adams</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus 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="Bis, Joshua C" sort="Bis, Joshua C" uniqKey="Bis J" first="Joshua C" last="Bis">Joshua C. Bis</name>
<affiliation wicri:level="4"><nlm:affiliation>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Cardiovascular Health Research Unit, Department of Medicine, 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="Weinstein, Galit" sort="Weinstein, Galit" uniqKey="Weinstein G" first="Galit" last="Weinstein">Galit Weinstein</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yu, Lei" sort="Yu, Lei" uniqKey="Yu L" first="Lei" last="Yu">Lei Yu</name>
<affiliation wicri:level="2"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL</wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Toglhofer, Anna Maria" sort="Toglhofer, Anna Maria" uniqKey="Toglhofer A" first="Anna Maria" last="Töglhofer">Anna Maria Töglhofer</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz</wicri:regionArea>
<wicri:noRegion>Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Smith, Albert Vernon" sort="Smith, Albert Vernon" uniqKey="Smith A" first="Albert Vernon" last="Smith">Albert Vernon Smith</name>
<affiliation wicri:level="1"><nlm:affiliation>Icelandic Heart Association, Iceland; Department of Medicine, University of Iceland, Reykjavik, Iceland.</nlm:affiliation>
<country xml:lang="fr">Islande</country>
<wicri:regionArea>Icelandic Heart Association, Iceland; Department of Medicine, University of Iceland, Reykjavik</wicri:regionArea>
<wicri:noRegion>Reykjavik</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Van Der Lee, Sven J" sort="Van Der Lee, Sven J" uniqKey="Van Der Lee S" first="Sven J" last="Van Der Lee">Sven J. Van Der Lee</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus 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="Gottesman, Rebecca F" sort="Gottesman, Rebecca F" uniqKey="Gottesman R" first="Rebecca F" last="Gottesman">Rebecca F. Gottesman</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Neurology, Johns Hopkins School of Medicine, Baltimore, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Johns Hopkins School of Medicine, Baltimore, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore</wicri:regionArea>
<placeName><settlement type="city">Baltimore</settlement>
<region type="state">Maryland</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Thomson, Russell" sort="Thomson, Russell" uniqKey="Thomson R" first="Russell" last="Thomson">Russell Thomson</name>
<affiliation wicri:level="1"><nlm:affiliation>Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania</wicri:regionArea>
<wicri:noRegion>Tasmania</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wang, Jing" sort="Wang, Jing" uniqKey="Wang J" first="Jing" last="Wang">Jing Wang</name>
<affiliation wicri:level="2"><nlm:affiliation>The Framingham Heart Study, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Framingham Heart Study, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, Qiong" sort="Yang, Qiong" uniqKey="Yang Q" first="Qiong" last="Yang">Qiong Yang</name>
<affiliation wicri:level="2"><nlm:affiliation>The Framingham Heart Study, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Framingham Heart Study, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</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:affiliation>Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Radiology, Erasmus 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="Lopez, Oscar L" sort="Lopez, Oscar L" uniqKey="Lopez O" first="Oscar L" last="Lopez">Oscar L. Lopez</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Becker, James T" sort="Becker, James T" uniqKey="Becker J" first="James T" last="Becker">James T. Becker</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, PA</wicri:regionArea>
<placeName><region type="state">Pennsylvanie</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Phan, Thanh G" sort="Phan, Thanh G" uniqKey="Phan T" first="Thanh G" last="Phan">Thanh G. Phan</name>
<affiliation wicri:level="1"><nlm:affiliation>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Beare, Richard J" sort="Beare, Richard J" uniqKey="Beare R" first="Richard J" last="Beare">Richard J. Beare</name>
<affiliation wicri:level="1"><nlm:affiliation>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Developmental Imaging Group, Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Developmental Imaging Group, Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria</wicri:regionArea>
<wicri:noRegion>Victoria</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Arfanakis, Konstantinos" sort="Arfanakis, Konstantinos" uniqKey="Arfanakis K" first="Konstantinos" last="Arfanakis">Konstantinos Arfanakis</name>
<affiliation wicri:level="2"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL</wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fleischman, Debra" sort="Fleischman, Debra" uniqKey="Fleischman D" first="Debra" last="Fleischman">Debra Fleischman</name>
<affiliation wicri:level="2"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL</wicri:regionArea>
<placeName><region type="state">Illinois</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:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus 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="Mazoyer, Bernard" sort="Mazoyer, Bernard" uniqKey="Mazoyer B" first="Bernard" last="Mazoyer">Bernard Mazoyer</name>
<affiliation wicri:level="4"><nlm:affiliation>Groupe d'Imagerie Neurofonctionnelle, UMR5296, CNRS, CEA, Université de Bordeaux, Bordeaux, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Groupe d'Imagerie Neurofonctionnelle, UMR5296, CNRS, CEA, Université de Bordeaux, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
<settlement type="city">Bordeaux</settlement>
</placeName>
<orgName type="university">Université de Bordeaux</orgName>
</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:affiliation>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz</wicri:regionArea>
<wicri:noRegion>Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Srikanth, Velandai" sort="Srikanth, Velandai" uniqKey="Srikanth V" first="Velandai" last="Srikanth">Velandai Srikanth</name>
<affiliation wicri:level="1"><nlm:affiliation>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</nlm:affiliation>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania</wicri:regionArea>
<wicri:noRegion>Tasmania</wicri:noRegion>
</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:affiliation>Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN</wicri:regionArea>
<placeName><region type="state">Minnesota</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:affiliation>Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN</wicri:regionArea>
<placeName><region type="state">Minnesota</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Amouyel, Philippe" sort="Amouyel, Philippe" uniqKey="Amouyel P" first="Philippe" last="Amouyel">Philippe Amouyel</name>
<affiliation wicri:level="4"><nlm:affiliation>Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France; INSERM, U744, Lille, France; Université Lille 2, Lille, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France; INSERM, U744, Lille, France; Université Lille 2, Lille</wicri:regionArea>
<placeName><region type="region">Hauts-de-France</region>
<region type="old region">Nord-Pas-de-Calais</region>
<settlement type="city">Lille</settlement>
<settlement type="city">Lille</settlement>
</placeName>
<orgName type="university">Université Lille 2</orgName>
</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:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus 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="Decarli, Charles" sort="Decarli, Charles" uniqKey="Decarli C" first="Charles" last="Decarli">Charles Decarli</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, University of California at Davis, Davis, CA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, University of California at Davis, Davis, CA</wicri:regionArea>
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<affiliation wicri:level="3"><nlm:affiliation>INSERM U897, University of Bordeaux, Bordeaux, France.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U897, University of Bordeaux, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
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<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:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden, the Netherlands; Center for Medical Systems Biology, Leiden, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden, the Netherlands; Center for Medical Systems Biology, Leiden</wicri:regionArea>
<placeName><settlement type="city">Leyde</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
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<author><name sortKey="Bennett, David A" sort="Bennett, David A" uniqKey="Bennett D" first="David A" last="Bennett">David A. Bennett</name>
<affiliation wicri:level="2"><nlm:affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL</wicri:regionArea>
<placeName><region type="state">Illinois</region>
</placeName>
</affiliation>
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<author><name sortKey="Schmidt, Reinhold" sort="Schmidt, Reinhold" uniqKey="Schmidt R" first="Reinhold" last="Schmidt">Reinhold Schmidt</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz, Austria.</nlm:affiliation>
<country xml:lang="fr">Autriche</country>
<wicri:regionArea>Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz</wicri:regionArea>
<wicri:noRegion>Medical University of Graz</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Longstreth, William T" sort="Longstreth, William T" uniqKey="Longstreth W" first="William T" last="Longstreth">William T. Longstreth</name>
<affiliation wicri:level="4"><nlm:affiliation>Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments 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>
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<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:affiliation>Department of Medicine-Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson, MS, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Medicine-Geriatrics/Gerontology, University of Mississippi Medical Center, Jackson, MS</wicri:regionArea>
<placeName><region type="state">État du Mississippi</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Fornage, Myriam" sort="Fornage, Myriam" uniqKey="Fornage M" first="Myriam" last="Fornage">Myriam Fornage</name>
<affiliation wicri:level="3"><nlm:affiliation>The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>The Human Genetics Center and Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston</wicri:regionArea>
<placeName><settlement type="city">Houston</settlement>
<region type="state">Texas</region>
</placeName>
</affiliation>
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<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:affiliation>Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Laboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD</wicri:regionArea>
<placeName><region type="state">Maryland</region>
</placeName>
</affiliation>
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<author><name sortKey="Seshadri, Sudha" sort="Seshadri, Sudha" uniqKey="Seshadri S" first="Sudha" last="Seshadri">Sudha Seshadri</name>
<affiliation wicri:level="2"><nlm:affiliation>Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Boston, MA, USA.</nlm:affiliation>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Boston, MA</wicri:regionArea>
<placeName><region type="state">Massachusetts</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Ikram, M Arfan" sort="Ikram, M Arfan" uniqKey="Ikram M" first="M Arfan" last="Ikram">M Arfan Ikram</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden, the Netherlands.</nlm:affiliation>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden</wicri:regionArea>
<placeName><settlement type="city">Leyde</settlement>
<region nuts="2" type="province">Hollande-Méridionale</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Debette, Stephanie" sort="Debette, Stephanie" uniqKey="Debette S" first="Stephanie" last="Debette">Stephanie Debette</name>
<affiliation wicri:level="3"><nlm:affiliation>INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux, France; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Bordeaux University Hospital, Bordeaux, France. Electronic address: sdebette@bu.edu.</nlm:affiliation>
<country xml:lang="fr">France</country>
<wicri:regionArea>INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux, France; Department of Neurology, Boston University School of Medicine, Boston, MA, USA; Department of Neurology, Bordeaux University Hospital, Bordeaux</wicri:regionArea>
<placeName><region type="region">Nouvelle-Aquitaine</region>
<region type="old region">Aquitaine</region>
<settlement type="city">Bordeaux</settlement>
</placeName>
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<series><title level="j">Neurobiology of aging</title>
<idno type="eISSN">1558-1497</idno>
<imprint><date when="2015" type="published">2015</date>
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<term>Aging (pathology)</term>
<term>Alleles</term>
<term>Alzheimer Disease (genetics)</term>
<term>Alzheimer Disease (pathology)</term>
<term>Apolipoproteins E (genetics)</term>
<term>Brain (pathology)</term>
<term>Female</term>
<term>Genome-Wide Association Study</term>
<term>Hippocampus (pathology)</term>
<term>Humans</term>
<term>Magnetic Resonance Imaging</term>
<term>Male</term>
<term>Organ Size (genetics)</term>
<term>Polymorphism, Single Nucleotide</term>
<term>Risk</term>
<term>Sialic Acid Binding Ig-like Lectin 3 (genetics)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Allèles</term>
<term>Apolipoprotéines E (génétique)</term>
<term>Encéphale (anatomopathologie)</term>
<term>Femelle</term>
<term>Hippocampe (anatomopathologie)</term>
<term>Humains</term>
<term>Imagerie par résonance magnétique</term>
<term>Lectine-3 de type Ig liant l'acide sialique (génétique)</term>
<term>Maladie d'Alzheimer (anatomopathologie)</term>
<term>Maladie d'Alzheimer (génétique)</term>
<term>Mâle</term>
<term>Polymorphisme de nucléotide simple</term>
<term>Risque</term>
<term>Taille d'organe (génétique)</term>
<term>Vieillissement (anatomopathologie)</term>
<term>Vieillissement (génétique)</term>
<term>Étude d'association pangénomique</term>
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<term>Sialic Acid Binding Ig-like Lectin 3</term>
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<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Encéphale</term>
<term>Hippocampe</term>
<term>Maladie d'Alzheimer</term>
<term>Vieillissement</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Aging</term>
<term>Alzheimer Disease</term>
<term>Organ Size</term>
</keywords>
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<term>Lectine-3 de type Ig liant l'acide sialique</term>
<term>Maladie d'Alzheimer</term>
<term>Taille d'organe</term>
<term>Vieillissement</term>
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<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Aging</term>
<term>Alzheimer Disease</term>
<term>Brain</term>
<term>Hippocampus</term>
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<term>Imagerie par résonance magnétique</term>
<term>Mâle</term>
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<front><div type="abstract" xml:lang="en">Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25670335</PMID>
<DateCreated><Year>2015</Year>
<Month>03</Month>
<Day>27</Day>
</DateCreated>
<DateCompleted><Year>2016</Year>
<Month>03</Month>
<Day>17</Day>
</DateCompleted>
<DateRevised><Year>2017</Year>
<Month>09</Month>
<Day>12</Day>
</DateRevised>
<Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1558-1497</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>36</Volume>
<Issue>4</Issue>
<PubDate><Year>2015</Year>
<Month>Apr</Month>
</PubDate>
</JournalIssue>
<Title>Neurobiology of aging</Title>
<ISOAbbreviation>Neurobiol. Aging</ISOAbbreviation>
</Journal>
<ArticleTitle>Association of Alzheimer's disease GWAS loci with MRI markers of brain aging.</ArticleTitle>
<Pagination><MedlinePgn>1765.e7-1765.e16</MedlinePgn>
</Pagination>
<ELocationID EIdType="pii" ValidYN="Y">S0197-4580(14)00845-8</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1016/j.neurobiolaging.2014.12.028</ELocationID>
<Abstract><AbstractText>Whether novel risk variants of Alzheimer's disease (AD) identified through genome-wide association studies also influence magnetic resonance imaging-based intermediate phenotypes of AD in the general population is unclear. We studied association of 24 AD risk loci with intracranial volume, total brain volume, hippocampal volume (HV), white matter hyperintensity burden, and brain infarcts in a meta-analysis of genetic association studies from large population-based samples (N = 8175-11,550). In single-SNP based tests, AD risk allele of APOE (rs2075650) was associated with smaller HV (p = 0.0054) and CD33 (rs3865444) with smaller intracranial volume (p = 0.0058). In gene-based tests, there was associations of HLA-DRB1 with total brain volume (p = 0.0006) and BIN1 with HV (p = 0.00089). A weighted AD genetic risk score was associated with smaller HV (beta ± SE = -0.047 ± 0.013, p = 0.00041), even after excluding the APOE locus (p = 0.029). However, only association of AD genetic risk score with HV, including APOE, was significant after multiple testing correction (including number of independent phenotypes tested). These results suggest that novel AD genetic risk variants may contribute to structural brain aging in nondemented older community persons.</AbstractText>
<CopyrightInformation>Copyright © 2015 Elsevier Inc. All rights reserved.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Chauhan</LastName>
<ForeName>Ganesh</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>INSERM U897, University of Bordeaux, Bordeaux, France; University of Bordeaux, Bordeaux, FranceINSERM U897, University of Bordeaux, Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Adams</LastName>
<ForeName>Hieab H H</ForeName>
<Initials>HHH</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bis</LastName>
<ForeName>Joshua C</ForeName>
<Initials>JC</Initials>
<AffiliationInfo><Affiliation>Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Weinstein</LastName>
<ForeName>Galit</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Boston University School of Medicine, Boston, MA, USA; The Framingham Heart Study, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yu</LastName>
<ForeName>Lei</ForeName>
<Initials>L</Initials>
<AffiliationInfo><Affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Töglhofer</LastName>
<ForeName>Anna Maria</ForeName>
<Initials>AM</Initials>
<AffiliationInfo><Affiliation>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Smith</LastName>
<ForeName>Albert Vernon</ForeName>
<Initials>AV</Initials>
<AffiliationInfo><Affiliation>Icelandic Heart Association, Iceland; Department of Medicine, University of Iceland, Reykjavik, Iceland.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>van der Lee</LastName>
<ForeName>Sven J</ForeName>
<Initials>SJ</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Gottesman</LastName>
<ForeName>Rebecca F</ForeName>
<Initials>RF</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Johns Hopkins School of Medicine, Baltimore, USA; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Thomson</LastName>
<ForeName>Russell</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Wang</LastName>
<ForeName>Jing</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>The Framingham Heart Study, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Qiong</ForeName>
<Initials>Q</Initials>
<AffiliationInfo><Affiliation>The Framingham Heart Study, Boston, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Niessen</LastName>
<ForeName>Wiro J</ForeName>
<Initials>WJ</Initials>
<AffiliationInfo><Affiliation>Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lopez</LastName>
<ForeName>Oscar L</ForeName>
<Initials>OL</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Becker</LastName>
<ForeName>James T</ForeName>
<Initials>JT</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychiatry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA; Department of Psychology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Phan</LastName>
<ForeName>Thanh G</ForeName>
<Initials>TG</Initials>
<AffiliationInfo><Affiliation>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Beare</LastName>
<ForeName>Richard J</ForeName>
<Initials>RJ</Initials>
<AffiliationInfo><Affiliation>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Developmental Imaging Group, Murdoch Childrens Research Institute, The Royal Children's Hospital, Parkville, Victoria, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Arfanakis</LastName>
<ForeName>Konstantinos</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Fleischman</LastName>
<ForeName>Debra</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Vernooij</LastName>
<ForeName>Meike W</ForeName>
<Initials>MW</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Department of Radiology, Erasmus Medical Center, Rotterdam, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Mazoyer</LastName>
<ForeName>Bernard</ForeName>
<Initials>B</Initials>
<AffiliationInfo><Affiliation>Groupe d'Imagerie Neurofonctionnelle, UMR5296, CNRS, CEA, Université de Bordeaux, Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schmidt</LastName>
<ForeName>Helena</ForeName>
<Initials>H</Initials>
<AffiliationInfo><Affiliation>Institute of Molecular Biology and Biochemistry, Centre for Molecular Medicine, Medical University of Graz, Graz, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Srikanth</LastName>
<ForeName>Velandai</ForeName>
<Initials>V</Initials>
<AffiliationInfo><Affiliation>Stroke and Ageing Research Centre, Southern Clinical School, Department of Medicine, Monash University, Melbourne, Victoria, Australia; Menzies Research Institute Tasmania, University of Tasmania, Hobart, Tasmania, Australia.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Knopman</LastName>
<ForeName>David S</ForeName>
<Initials>DS</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Jack</LastName>
<ForeName>Clifford R</ForeName>
<Initials>CR</Initials>
<Suffix>Jr</Suffix>
<AffiliationInfo><Affiliation>Department of Radiology, Mayo Clinic College of Medicine, Rochester, MN, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Amouyel</LastName>
<ForeName>Philippe</ForeName>
<Initials>P</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France; INSERM, U744, Lille, France; Université Lille 2, Lille, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Hofman</LastName>
<ForeName>Albert</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>DeCarli</LastName>
<ForeName>Charles</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, University of California at Davis, Davis, CA, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Tzourio</LastName>
<ForeName>Christophe</ForeName>
<Initials>C</Initials>
<AffiliationInfo><Affiliation>INSERM U897, University of Bordeaux, Bordeaux, France.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>van Duijn</LastName>
<ForeName>Cornelia M</ForeName>
<Initials>CM</Initials>
<AffiliationInfo><Affiliation>Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands; Netherlands Consortium for Healthy Aging, Leiden, the Netherlands; Center for Medical Systems Biology, Leiden, the Netherlands.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Bennett</LastName>
<ForeName>David A</ForeName>
<Initials>DA</Initials>
<AffiliationInfo><Affiliation>Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA; Department of Neurological Sciences, Rush University Medical Center, Chicago, IL, USA.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Schmidt</LastName>
<ForeName>Reinhold</ForeName>
<Initials>R</Initials>
<AffiliationInfo><Affiliation>Department of Neurology, Clinical Division of Neurogeriatrics, Medical University of Graz, Austria.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Longstreth</LastName>
<ForeName>William T</ForeName>
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