Identification of common variants associated with human hippocampal and intracranial volumes
Identifieur interne : 004B46 ( PascalFrancis/Curation ); précédent : 004B45; suivant : 004B47Identification of common variants associated with human hippocampal and intracranial volumes
Auteurs : Jason L. Stein [États-Unis] ; Sarah E. Medland [Australie, États-Unis] ; Alejandro Arias Vasquez [Pays-Bas] ; Derrek P. Hibar [États-Unis] ; Rudy E. Senstad [États-Unis] ; Anderson M. Winkler [États-Unis] ; Roberto Toro [France] ; Katja Appel [Allemagne] ; Richard Bartecek [Pays-Bas] ; Rjan Bergmann [Norvège] ; Manon Bernard [Canada] ; Andrew A. Brown [Norvège] ; Dara M. Cannon [Irlande (pays)] ; M. Mallar Chakravarty [Canada] ; Andrea Christoforou [Norvège] ; Martin Domin [Allemagne] ; Oliver Grimm [Allemagne] ; Marisa Hollinshead ; Avram J. Holmes ; Georg Homuth ; Jouke-Jan Hottenga ; Camilla Langan [Irlande (pays)] ; Lorna M. Lopez ; Narelle K. Hansell [Australie] ; Kristy S. Hwang [États-Unis] ; Sungeun Kim ; Gonzalo Laje ; Phil H. Lee ; XINMIN LIU ; Eva Loth ; Anbarasu Lourdusamy ; Morten Mattingsdal [Norvège] ; Sebastian Mohnke ; Susana Munoz Maniega ; Kwangsik Nho ; Allison C. Nugent ; Carol O'Brien ; Martina Papmeyer ; Benno Pütz ; Adaikalavan Ramasamy ; Jerod Rasmussen ; Mark Rijpkema [Pays-Bas] ; Shannon L. Risacher ; J. Cooper Roddey ; Emma J. Rose ; Mina Ryten ; LI SHEN ; Emma Sprooten ; Eric Strengman ; Alexander Teumer ; Daniah Trabzuni ; Jessica Turner ; Kristel Van Eijk ; Theo G. M Van Erp ; Marie-Jose Van Tol ; Katharina Wittfeld [Allemagne] ; Christiane Wolf ; Saskia Woudstra ; Andre Aleman ; Saud AlhusainiSource :
- Nature genetics [ 1061-4036 ] ; 2012.
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Abstract
Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease1,2 and is reduced in schizophrenia3, major depression4 and mesial temporal lobe epilepsy5. Whereas many brain imaging phenotypes are highly heritable6,7, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10-16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10-12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1 q23.3; N = 6,500; P = 5.81 × 10-7).
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Cannon</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Clinical Neuroimaging Laboratory, Department of Anatomy, National University of Ireland Galway</s1><s2>Galway</s2><s3>IRL</s3><sZ>13 aut.</sZ></inist:fA14><country>Irlande (pays)</country></affiliation></author><author><name sortKey="Mallar Chakravarty, M" sort="Mallar Chakravarty, M" uniqKey="Mallar Chakravarty M" first="M." last="Mallar Chakravarty">M. Mallar Chakravarty</name><affiliation wicri:level="1"><inist:fA14 i1="21"><s1>Rotman Research Institute, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>14 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Christoforou, Andrea" sort="Christoforou, Andrea" uniqKey="Christoforou A" first="Andrea" last="Christoforou">Andrea Christoforou</name><affiliation wicri:level="1"><inist:fA14 i1="22"><s1>Dr Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen</s1><s2>Bergen</s2><s3>NOR</s3><sZ>15 aut.</sZ></inist:fA14><country>Norvège</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="23"><s1>Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</s1><s2>Bergen</s2><s3>NOR</s3><sZ>15 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Domin, Martin" sort="Domin, Martin" uniqKey="Domin M" first="Martin" last="Domin">Martin Domin</name><affiliation wicri:level="1"><inist:fA14 i1="24"><s1>Department of Diagnostic Radiology and Neuroradiology, University of Greifswald</s1><s2>Greifswald</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Grimm, Oliver" sort="Grimm, Oliver" uniqKey="Grimm O" first="Oliver" last="Grimm">Oliver Grimm</name><affiliation wicri:level="1"><inist:fA14 i1="25"><s1>Central Institute of Mental Health, University of Heidelberg-Medical Faculty Mannheim</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>17 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Hollinshead, Marisa" sort="Hollinshead, Marisa" uniqKey="Hollinshead M" first="Marisa" last="Hollinshead">Marisa Hollinshead</name></author><author><name sortKey="Holmes, Avram J" sort="Holmes, Avram J" uniqKey="Holmes A" first="Avram J." last="Holmes">Avram J. Holmes</name></author><author><name sortKey="Homuth, Georg" sort="Homuth, Georg" uniqKey="Homuth G" first="Georg" last="Homuth">Georg Homuth</name></author><author><name sortKey="Hottenga, Jouke Jan" sort="Hottenga, Jouke Jan" uniqKey="Hottenga J" first="Jouke-Jan" last="Hottenga">Jouke-Jan Hottenga</name></author><author><name sortKey="Langan, Camilla" sort="Langan, Camilla" uniqKey="Langan C" first="Camilla" last="Langan">Camilla Langan</name><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Clinical Neuroimaging Laboratory, Department of Psychiatry, National University of Ireland Galway</s1><s2>Galway</s2><s3>IRL</s3><sZ>22 aut.</sZ></inist:fA14><country>Irlande (pays)</country></affiliation></author><author><name sortKey="Lopez, Lorna M" sort="Lopez, Lorna M" uniqKey="Lopez L" first="Lorna M." last="Lopez">Lorna M. Lopez</name></author><author><name sortKey="Hansell, Narelle K" sort="Hansell, Narelle K" uniqKey="Hansell N" first="Narelle K." last="Hansell">Narelle K. Hansell</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane, Queensland</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Hwang, Kristy S" sort="Hwang, Kristy S" uniqKey="Hwang K" first="Kristy S." last="Hwang">Kristy S. Hwang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California</s1><s2>Los Angeles, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Kim, Sungeun" sort="Kim, Sungeun" uniqKey="Kim S" first="Sungeun" last="Kim">Sungeun Kim</name></author><author><name sortKey="Laje, Gonzalo" sort="Laje, Gonzalo" uniqKey="Laje G" first="Gonzalo" last="Laje">Gonzalo Laje</name></author><author><name sortKey="Lee, Phil H" sort="Lee, Phil H" uniqKey="Lee P" first="Phil H." last="Lee">Phil H. Lee</name></author><author><name sortKey="Xinmin Liu" sort="Xinmin Liu" uniqKey="Xinmin Liu" last="Xinmin Liu">XINMIN LIU</name></author><author><name sortKey="Loth, Eva" sort="Loth, Eva" uniqKey="Loth E" first="Eva" last="Loth">Eva Loth</name></author><author><name sortKey="Lourdusamy, Anbarasu" sort="Lourdusamy, Anbarasu" uniqKey="Lourdusamy A" first="Anbarasu" last="Lourdusamy">Anbarasu Lourdusamy</name></author><author><name sortKey="Mattingsdal, Morten" sort="Mattingsdal, Morten" uniqKey="Mattingsdal M" first="Morten" last="Mattingsdal">Morten Mattingsdal</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Institute of Clinical Medicine, University of Oslo</s1><s2>Oslo</s2><s3>NOR</s3><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>32 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Mohnke, Sebastian" sort="Mohnke, Sebastian" uniqKey="Mohnke S" first="Sebastian" last="Mohnke">Sebastian Mohnke</name></author><author><name sortKey="Munoz Maniega, Susana" sort="Munoz Maniega, Susana" uniqKey="Munoz Maniega S" first="Susana" last="Munoz Maniega">Susana Munoz Maniega</name></author><author><name sortKey="Nho, Kwangsik" sort="Nho, Kwangsik" uniqKey="Nho K" first="Kwangsik" last="Nho">Kwangsik Nho</name></author><author><name sortKey="Nugent, Allison C" sort="Nugent, Allison C" uniqKey="Nugent A" first="Allison C." last="Nugent">Allison C. Nugent</name></author><author><name sortKey="O Brien, Carol" sort="O Brien, Carol" uniqKey="O Brien C" first="Carol" last="O'Brien">Carol O'Brien</name></author><author><name sortKey="Papmeyer, Martina" sort="Papmeyer, Martina" uniqKey="Papmeyer M" first="Martina" last="Papmeyer">Martina Papmeyer</name></author><author><name sortKey="Putz, Benno" sort="Putz, Benno" uniqKey="Putz B" first="Benno" last="Pütz">Benno Pütz</name></author><author><name sortKey="Ramasamy, Adaikalavan" sort="Ramasamy, Adaikalavan" uniqKey="Ramasamy A" first="Adaikalavan" last="Ramasamy">Adaikalavan Ramasamy</name></author><author><name sortKey="Rasmussen, Jerod" sort="Rasmussen, Jerod" uniqKey="Rasmussen J" first="Jerod" last="Rasmussen">Jerod Rasmussen</name></author><author><name sortKey="Rijpkema, Mark" sort="Rijpkema, Mark" uniqKey="Rijpkema M" first="Mark" last="Rijpkema">Mark Rijpkema</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ><sZ>42 aut.</sZ></inist:fA14><country>Pays-Bas</country></affiliation></author><author><name sortKey="Risacher, Shannon L" sort="Risacher, Shannon L" uniqKey="Risacher S" first="Shannon L." last="Risacher">Shannon L. Risacher</name></author><author><name sortKey="Cooper Roddey, J" sort="Cooper Roddey, J" uniqKey="Cooper Roddey J" first="J." last="Cooper Roddey">J. Cooper Roddey</name></author><author><name sortKey="Rose, Emma J" sort="Rose, Emma J" uniqKey="Rose E" first="Emma J." last="Rose">Emma J. Rose</name></author><author><name sortKey="Ryten, Mina" sort="Ryten, Mina" uniqKey="Ryten M" first="Mina" last="Ryten">Mina Ryten</name></author><author><name sortKey="Li Shen" sort="Li Shen" uniqKey="Li Shen" last="Li Shen">LI SHEN</name></author><author><name sortKey="Sprooten, Emma" sort="Sprooten, Emma" uniqKey="Sprooten E" first="Emma" last="Sprooten">Emma Sprooten</name></author><author><name sortKey="Strengman, Eric" sort="Strengman, Eric" uniqKey="Strengman E" first="Eric" last="Strengman">Eric Strengman</name></author><author><name sortKey="Teumer, Alexander" sort="Teumer, Alexander" uniqKey="Teumer A" first="Alexander" last="Teumer">Alexander Teumer</name></author><author><name sortKey="Trabzuni, Daniah" sort="Trabzuni, Daniah" uniqKey="Trabzuni D" first="Daniah" last="Trabzuni">Daniah Trabzuni</name></author><author><name sortKey="Turner, Jessica" sort="Turner, Jessica" uniqKey="Turner J" first="Jessica" last="Turner">Jessica Turner</name></author><author><name sortKey="Eijk, Kristel Van" sort="Eijk, Kristel Van" uniqKey="Eijk K" first="Kristel Van" last="Eijk">Kristel Van Eijk</name></author><author><name sortKey="Erp, Theo G M Van" sort="Erp, Theo G M Van" uniqKey="Erp T" first="Theo G. M Van" last="Erp">Theo G. M Van Erp</name></author><author><name sortKey="Tol, Marie Jose Van" sort="Tol, Marie Jose Van" uniqKey="Tol M" first="Marie-Jose Van" last="Tol">Marie-Jose Van Tol</name></author><author><name sortKey="Wittfeld, Katharina" sort="Wittfeld, Katharina" uniqKey="Wittfeld K" first="Katharina" last="Wittfeld">Katharina Wittfeld</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Psychiatry and Psychotherapy, University of Greifswald</s1><s2>Greifswald</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>56 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Wolf, Christiane" sort="Wolf, Christiane" uniqKey="Wolf C" first="Christiane" last="Wolf">Christiane Wolf</name></author><author><name sortKey="Woudstra, Saskia" sort="Woudstra, Saskia" uniqKey="Woudstra S" first="Saskia" last="Woudstra">Saskia Woudstra</name></author><author><name sortKey="Aleman, Andre" sort="Aleman, Andre" uniqKey="Aleman A" first="Andre" last="Aleman">Andre Aleman</name></author><author><name sortKey="Alhusaini, Saud" sort="Alhusaini, Saud" uniqKey="Alhusaini S" first="Saud" last="Alhusaini">Saud Alhusaini</name></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">12-0224071</idno><date when="2012">2012</date><idno type="stanalyst">PASCAL 12-0224071 INIST</idno><idno type="RBID">Pascal:12-0224071</idno><idno type="wicri:Area/PascalFrancis/Corpus">001368</idno><idno type="wicri:Area/PascalFrancis/Curation">004B46</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Identification of common variants associated with human hippocampal and intracranial volumes</title><author><name sortKey="Stein, Jason L" sort="Stein, Jason L" uniqKey="Stein J" first="Jason L." last="Stein">Jason L. Stein</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California</s1><s2>Los Angeles, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Medland, Sarah E" sort="Medland, Sarah E" uniqKey="Medland S" first="Sarah E." last="Medland">Sarah E. Medland</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane, Queensland</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Quantitative Genetics Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane, Queensland</s2><s3>AUS</s3><sZ>2 aut.</sZ></inist:fA14><country>Australie</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Broad Institute of Harvard University and MIT</s1><s2>Cambridge, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Arias Vasquez, Alejandro" sort="Arias Vasquez, Alejandro" uniqKey="Arias Vasquez A" first="Alejandro" last="Arias Vasquez">Alejandro Arias Vasquez</name><affiliation wicri:level="1"><inist:fA14 i1="05"><s1>Department of Human Genetics, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ></inist:fA14><country>Pays-Bas</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Department of Psychiatry, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ></inist:fA14><country>Pays-Bas</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ><sZ>42 aut.</sZ></inist:fA14><country>Pays-Bas</country></affiliation></author><author><name sortKey="Hibar, Derrek P" sort="Hibar, Derrek P" uniqKey="Hibar D" first="Derrek P." last="Hibar">Derrek P. Hibar</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California</s1><s2>Los Angeles, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Senstad, Rudy E" sort="Senstad, Rudy E" uniqKey="Senstad R" first="Rudy E." last="Senstad">Rudy E. Senstad</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California</s1><s2>Los Angeles, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Winkler, Anderson M" sort="Winkler, Anderson M" uniqKey="Winkler A" first="Anderson M." last="Winkler">Anderson M. Winkler</name><affiliation wicri:level="1"><inist:fA14 i1="08"><s1>Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital</s1><s2>Hartford, Connecticut</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="09"><s1>Department of Psychiatry, Yale University School of Medicine</s1><s2>New Haven, Connecticut</s2><s3>USA</s3><sZ>6 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Toro, Roberto" sort="Toro, Roberto" uniqKey="Toro R" first="Roberto" last="Toro">Roberto Toro</name><affiliation wicri:level="1"><inist:fA14 i1="10"><s1>Laboratory of Human Genetics and Cognitive Functions, Institut Pasteur</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="11"><s1>Centre Nationale de Recherche Scientifique (CNRS) Unité de Recherche Associee (URA) 2182 Genes, Synapses and Cognition, Institut Pasteur</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></inist:fA14><country>France</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="12"><s1>Department of Neuroscience, Université Paris Diderot, Sorbonne Paris Cite</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></inist:fA14><country>France</country></affiliation></author><author><name sortKey="Appel, Katja" sort="Appel, Katja" uniqKey="Appel K" first="Katja" last="Appel">Katja Appel</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Psychiatry and Psychotherapy, University of Greifswald</s1><s2>Greifswald</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>56 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="14"><s1>Institute of Psychology, Department of Clinical Psychology and Psychotherapy, University of Heidelberg</s1><s2>Heidelberg</s2><s3>DEU</s3><sZ>8 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Bartecek, Richard" sort="Bartecek, Richard" uniqKey="Bartecek R" first="Richard" last="Bartecek">Richard Bartecek</name><affiliation wicri:level="1"><inist:fA14 i1="15"><s1>Department of Psychiatry, Rudolf Magnus Institute, University Medical Center Utrecht</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>9 aut.</sZ></inist:fA14><country>Pays-Bas</country></affiliation></author><author><name sortKey="Bergmann, Rjan" sort="Bergmann, Rjan" uniqKey="Bergmann " first=" Rjan" last="Bergmann"> Rjan Bergmann</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Institute of Clinical Medicine, University of Oslo</s1><s2>Oslo</s2><s3>NOR</s3><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>32 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Bernard, Manon" sort="Bernard, Manon" uniqKey="Bernard M" first="Manon" last="Bernard">Manon Bernard</name><affiliation wicri:level="1"><inist:fA14 i1="17"><s1>The Hospital for Sick Children, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>11 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Brown, Andrew A" sort="Brown, Andrew A" uniqKey="Brown A" first="Andrew A." last="Brown">Andrew A. Brown</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Institute of Clinical Medicine, University of Oslo</s1><s2>Oslo</s2><s3>NOR</s3><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>32 aut.</sZ></inist:fA14><country>Norvège</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="18"><s1>Institute of Basic Medical Sciences, Department of Biostatistics, University of Oslo</s1><s2>Oslo</s2><s3>NOR</s3><sZ>12 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Cannon, Dara M" sort="Cannon, Dara M" uniqKey="Cannon D" first="Dara M." last="Cannon">Dara M. Cannon</name><affiliation wicri:level="1"><inist:fA14 i1="19"><s1>Clinical Neuroimaging Laboratory, Department of Anatomy, National University of Ireland Galway</s1><s2>Galway</s2><s3>IRL</s3><sZ>13 aut.</sZ></inist:fA14><country>Irlande (pays)</country></affiliation></author><author><name sortKey="Mallar Chakravarty, M" sort="Mallar Chakravarty, M" uniqKey="Mallar Chakravarty M" first="M." last="Mallar Chakravarty">M. Mallar Chakravarty</name><affiliation wicri:level="1"><inist:fA14 i1="21"><s1>Rotman Research Institute, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>14 aut.</sZ></inist:fA14><country>Canada</country></affiliation></author><author><name sortKey="Christoforou, Andrea" sort="Christoforou, Andrea" uniqKey="Christoforou A" first="Andrea" last="Christoforou">Andrea Christoforou</name><affiliation wicri:level="1"><inist:fA14 i1="22"><s1>Dr Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen</s1><s2>Bergen</s2><s3>NOR</s3><sZ>15 aut.</sZ></inist:fA14><country>Norvège</country></affiliation><affiliation wicri:level="1"><inist:fA14 i1="23"><s1>Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</s1><s2>Bergen</s2><s3>NOR</s3><sZ>15 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Domin, Martin" sort="Domin, Martin" uniqKey="Domin M" first="Martin" last="Domin">Martin Domin</name><affiliation wicri:level="1"><inist:fA14 i1="24"><s1>Department of Diagnostic Radiology and Neuroradiology, University of Greifswald</s1><s2>Greifswald</s2><s3>DEU</s3><sZ>16 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Grimm, Oliver" sort="Grimm, Oliver" uniqKey="Grimm O" first="Oliver" last="Grimm">Oliver Grimm</name><affiliation wicri:level="1"><inist:fA14 i1="25"><s1>Central Institute of Mental Health, University of Heidelberg-Medical Faculty Mannheim</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>17 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Hollinshead, Marisa" sort="Hollinshead, Marisa" uniqKey="Hollinshead M" first="Marisa" last="Hollinshead">Marisa Hollinshead</name></author><author><name sortKey="Holmes, Avram J" sort="Holmes, Avram J" uniqKey="Holmes A" first="Avram J." last="Holmes">Avram J. Holmes</name></author><author><name sortKey="Homuth, Georg" sort="Homuth, Georg" uniqKey="Homuth G" first="Georg" last="Homuth">Georg Homuth</name></author><author><name sortKey="Hottenga, Jouke Jan" sort="Hottenga, Jouke Jan" uniqKey="Hottenga J" first="Jouke-Jan" last="Hottenga">Jouke-Jan Hottenga</name></author><author><name sortKey="Langan, Camilla" sort="Langan, Camilla" uniqKey="Langan C" first="Camilla" last="Langan">Camilla Langan</name><affiliation wicri:level="1"><inist:fA14 i1="20"><s1>Clinical Neuroimaging Laboratory, Department of Psychiatry, National University of Ireland Galway</s1><s2>Galway</s2><s3>IRL</s3><sZ>22 aut.</sZ></inist:fA14><country>Irlande (pays)</country></affiliation></author><author><name sortKey="Lopez, Lorna M" sort="Lopez, Lorna M" uniqKey="Lopez L" first="Lorna M." last="Lopez">Lorna M. Lopez</name></author><author><name sortKey="Hansell, Narelle K" sort="Hansell, Narelle K" uniqKey="Hansell N" first="Narelle K." last="Hansell">Narelle K. Hansell</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane, Queensland</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>24 aut.</sZ></inist:fA14><country>Australie</country></affiliation></author><author><name sortKey="Hwang, Kristy S" sort="Hwang, Kristy S" uniqKey="Hwang K" first="Kristy S." last="Hwang">Kristy S. Hwang</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California</s1><s2>Los Angeles, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>25 aut.</sZ></inist:fA14><country>États-Unis</country></affiliation></author><author><name sortKey="Kim, Sungeun" sort="Kim, Sungeun" uniqKey="Kim S" first="Sungeun" last="Kim">Sungeun Kim</name></author><author><name sortKey="Laje, Gonzalo" sort="Laje, Gonzalo" uniqKey="Laje G" first="Gonzalo" last="Laje">Gonzalo Laje</name></author><author><name sortKey="Lee, Phil H" sort="Lee, Phil H" uniqKey="Lee P" first="Phil H." last="Lee">Phil H. Lee</name></author><author><name sortKey="Xinmin Liu" sort="Xinmin Liu" uniqKey="Xinmin Liu" last="Xinmin Liu">XINMIN LIU</name></author><author><name sortKey="Loth, Eva" sort="Loth, Eva" uniqKey="Loth E" first="Eva" last="Loth">Eva Loth</name></author><author><name sortKey="Lourdusamy, Anbarasu" sort="Lourdusamy, Anbarasu" uniqKey="Lourdusamy A" first="Anbarasu" last="Lourdusamy">Anbarasu Lourdusamy</name></author><author><name sortKey="Mattingsdal, Morten" sort="Mattingsdal, Morten" uniqKey="Mattingsdal M" first="Morten" last="Mattingsdal">Morten Mattingsdal</name><affiliation wicri:level="1"><inist:fA14 i1="16"><s1>Institute of Clinical Medicine, University of Oslo</s1><s2>Oslo</s2><s3>NOR</s3><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>32 aut.</sZ></inist:fA14><country>Norvège</country></affiliation></author><author><name sortKey="Mohnke, Sebastian" sort="Mohnke, Sebastian" uniqKey="Mohnke S" first="Sebastian" last="Mohnke">Sebastian Mohnke</name></author><author><name sortKey="Munoz Maniega, Susana" sort="Munoz Maniega, Susana" uniqKey="Munoz Maniega S" first="Susana" last="Munoz Maniega">Susana Munoz Maniega</name></author><author><name sortKey="Nho, Kwangsik" sort="Nho, Kwangsik" uniqKey="Nho K" first="Kwangsik" last="Nho">Kwangsik Nho</name></author><author><name sortKey="Nugent, Allison C" sort="Nugent, Allison C" uniqKey="Nugent A" first="Allison C." last="Nugent">Allison C. Nugent</name></author><author><name sortKey="O Brien, Carol" sort="O Brien, Carol" uniqKey="O Brien C" first="Carol" last="O'Brien">Carol O'Brien</name></author><author><name sortKey="Papmeyer, Martina" sort="Papmeyer, Martina" uniqKey="Papmeyer M" first="Martina" last="Papmeyer">Martina Papmeyer</name></author><author><name sortKey="Putz, Benno" sort="Putz, Benno" uniqKey="Putz B" first="Benno" last="Pütz">Benno Pütz</name></author><author><name sortKey="Ramasamy, Adaikalavan" sort="Ramasamy, Adaikalavan" uniqKey="Ramasamy A" first="Adaikalavan" last="Ramasamy">Adaikalavan Ramasamy</name></author><author><name sortKey="Rasmussen, Jerod" sort="Rasmussen, Jerod" uniqKey="Rasmussen J" first="Jerod" last="Rasmussen">Jerod Rasmussen</name></author><author><name sortKey="Rijpkema, Mark" sort="Rijpkema, Mark" uniqKey="Rijpkema M" first="Mark" last="Rijpkema">Mark Rijpkema</name><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ><sZ>42 aut.</sZ></inist:fA14><country>Pays-Bas</country></affiliation></author><author><name sortKey="Risacher, Shannon L" sort="Risacher, Shannon L" uniqKey="Risacher S" first="Shannon L." last="Risacher">Shannon L. Risacher</name></author><author><name sortKey="Cooper Roddey, J" sort="Cooper Roddey, J" uniqKey="Cooper Roddey J" first="J." last="Cooper Roddey">J. Cooper Roddey</name></author><author><name sortKey="Rose, Emma J" sort="Rose, Emma J" uniqKey="Rose E" first="Emma J." last="Rose">Emma J. Rose</name></author><author><name sortKey="Ryten, Mina" sort="Ryten, Mina" uniqKey="Ryten M" first="Mina" last="Ryten">Mina Ryten</name></author><author><name sortKey="Li Shen" sort="Li Shen" uniqKey="Li Shen" last="Li Shen">LI SHEN</name></author><author><name sortKey="Sprooten, Emma" sort="Sprooten, Emma" uniqKey="Sprooten E" first="Emma" last="Sprooten">Emma Sprooten</name></author><author><name sortKey="Strengman, Eric" sort="Strengman, Eric" uniqKey="Strengman E" first="Eric" last="Strengman">Eric Strengman</name></author><author><name sortKey="Teumer, Alexander" sort="Teumer, Alexander" uniqKey="Teumer A" first="Alexander" last="Teumer">Alexander Teumer</name></author><author><name sortKey="Trabzuni, Daniah" sort="Trabzuni, Daniah" uniqKey="Trabzuni D" first="Daniah" last="Trabzuni">Daniah Trabzuni</name></author><author><name sortKey="Turner, Jessica" sort="Turner, Jessica" uniqKey="Turner J" first="Jessica" last="Turner">Jessica Turner</name></author><author><name sortKey="Eijk, Kristel Van" sort="Eijk, Kristel Van" uniqKey="Eijk K" first="Kristel Van" last="Eijk">Kristel Van Eijk</name></author><author><name sortKey="Erp, Theo G M Van" sort="Erp, Theo G M Van" uniqKey="Erp T" first="Theo G. M Van" last="Erp">Theo G. M Van Erp</name></author><author><name sortKey="Tol, Marie Jose Van" sort="Tol, Marie Jose Van" uniqKey="Tol M" first="Marie-Jose Van" last="Tol">Marie-Jose Van Tol</name></author><author><name sortKey="Wittfeld, Katharina" sort="Wittfeld, Katharina" uniqKey="Wittfeld K" first="Katharina" last="Wittfeld">Katharina Wittfeld</name><affiliation wicri:level="1"><inist:fA14 i1="13"><s1>Department of Psychiatry and Psychotherapy, University of Greifswald</s1><s2>Greifswald</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>56 aut.</sZ></inist:fA14><country>Allemagne</country></affiliation></author><author><name sortKey="Wolf, Christiane" sort="Wolf, Christiane" uniqKey="Wolf C" first="Christiane" last="Wolf">Christiane Wolf</name></author><author><name sortKey="Woudstra, Saskia" sort="Woudstra, Saskia" uniqKey="Woudstra S" first="Saskia" last="Woudstra">Saskia Woudstra</name></author><author><name sortKey="Aleman, Andre" sort="Aleman, Andre" uniqKey="Aleman A" first="Andre" last="Aleman">Andre Aleman</name></author><author><name sortKey="Alhusaini, Saud" sort="Alhusaini, Saud" uniqKey="Alhusaini S" first="Saud" last="Alhusaini">Saud Alhusaini</name></author></analytic><series><title level="j" type="main">Nature genetics</title><title level="j" type="abbreviated">Nat. genet.</title><idno type="ISSN">1061-4036</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Nature genetics</title><title level="j" type="abbreviated">Nat. genet.</title><idno type="ISSN">1061-4036</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Human</term><term>Identification</term><term>Intracranial</term><term>Variant</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Identification</term><term>Variant</term><term>Homme</term><term>Intracrânien</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease<sup>1,2</sup> and is reduced in schizophrenia<sup>3</sup>, major depression<sup>4</sup> and mesial temporal lobe epilepsy<sup>5</sup>. Whereas many brain imaging phenotypes are highly heritable<sup>6,7</sup>, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10<sup>-16</sup>) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10<sup>-12</sup>). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1 q23.3; N = 6,500; P = 5.81 × 10<sup>-7</sup>).</div></front></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>1061-4036</s0></fA01><fA02 i1="01"><s0>NGENEC</s0></fA02><fA03 i2="1"><s0>Nat. genet.</s0></fA03><fA05><s2>44</s2></fA05><fA06><s2>5</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Identification of common variants associated with human hippocampal and intracranial volumes</s1></fA08><fA11 i1="01" i2="1"><s1>STEIN (Jason L.)</s1></fA11><fA11 i1="02" i2="1"><s1>MEDLAND (Sarah E.)</s1></fA11><fA11 i1="03" i2="1"><s1>ARIAS VASQUEZ (Alejandro)</s1></fA11><fA11 i1="04" i2="1"><s1>HIBAR (Derrek P.)</s1></fA11><fA11 i1="05" i2="1"><s1>SENSTAD (Rudy E.)</s1></fA11><fA11 i1="06" i2="1"><s1>WINKLER (Anderson M.)</s1></fA11><fA11 i1="07" i2="1"><s1>TORO (Roberto)</s1></fA11><fA11 i1="08" i2="1"><s1>APPEL (Katja)</s1></fA11><fA11 i1="09" i2="1"><s1>BARTECEK (Richard)</s1></fA11><fA11 i1="10" i2="1"><s1>BERGMANN (Ørjan)</s1></fA11><fA11 i1="11" i2="1"><s1>BERNARD (Manon)</s1></fA11><fA11 i1="12" i2="1"><s1>BROWN (Andrew A.)</s1></fA11><fA11 i1="13" i2="1"><s1>CANNON (Dara M.)</s1></fA11><fA11 i1="14" i2="1"><s1>MALLAR CHAKRAVARTY (M.)</s1></fA11><fA11 i1="15" i2="1"><s1>CHRISTOFOROU (Andrea)</s1></fA11><fA11 i1="16" i2="1"><s1>DOMIN (Martin)</s1></fA11><fA11 i1="17" i2="1"><s1>GRIMM (Oliver)</s1></fA11><fA11 i1="18" i2="1"><s1>HOLLINSHEAD (Marisa)</s1></fA11><fA11 i1="19" i2="1"><s1>HOLMES (Avram J.)</s1></fA11><fA11 i1="20" i2="1"><s1>HOMUTH (Georg)</s1></fA11><fA11 i1="21" i2="1"><s1>HOTTENGA (Jouke-Jan)</s1></fA11><fA11 i1="22" i2="1"><s1>LANGAN (Camilla)</s1></fA11><fA11 i1="23" i2="1"><s1>LOPEZ (Lorna M.)</s1></fA11><fA11 i1="24" i2="1"><s1>HANSELL (Narelle K.)</s1></fA11><fA11 i1="25" i2="1"><s1>HWANG (Kristy S.)</s1></fA11><fA11 i1="26" i2="1"><s1>KIM (Sungeun)</s1></fA11><fA11 i1="27" i2="1"><s1>LAJE (Gonzalo)</s1></fA11><fA11 i1="28" i2="1"><s1>LEE (Phil H.)</s1></fA11><fA11 i1="29" i2="1"><s1>XINMIN LIU</s1></fA11><fA11 i1="30" i2="1"><s1>LOTH (Eva)</s1></fA11><fA11 i1="31" i2="1"><s1>LOURDUSAMY (Anbarasu)</s1></fA11><fA11 i1="32" i2="1"><s1>MATTINGSDAL (Morten)</s1></fA11><fA11 i1="33" i2="1"><s1>MOHNKE (Sebastian)</s1></fA11><fA11 i1="34" i2="1"><s1>MUNOZ MANIEGA (Susana)</s1></fA11><fA11 i1="35" i2="1"><s1>NHO (Kwangsik)</s1></fA11><fA11 i1="36" i2="1"><s1>NUGENT (Allison C.)</s1></fA11><fA11 i1="37" i2="1"><s1>O'BRIEN (Carol)</s1></fA11><fA11 i1="38" i2="1"><s1>PAPMEYER (Martina)</s1></fA11><fA11 i1="39" i2="1"><s1>PÜTZ (Benno)</s1></fA11><fA11 i1="40" i2="1"><s1>RAMASAMY (Adaikalavan)</s1></fA11><fA11 i1="41" i2="1"><s1>RASMUSSEN (Jerod)</s1></fA11><fA11 i1="42" i2="1"><s1>RIJPKEMA (Mark)</s1></fA11><fA11 i1="43" i2="1"><s1>RISACHER (Shannon L.)</s1></fA11><fA11 i1="44" i2="1"><s1>COOPER RODDEY (J.)</s1></fA11><fA11 i1="45" i2="1"><s1>ROSE (Emma J.)</s1></fA11><fA11 i1="46" i2="1"><s1>RYTEN (Mina)</s1></fA11><fA11 i1="47" i2="1"><s1>LI SHEN</s1></fA11><fA11 i1="48" i2="1"><s1>SPROOTEN (Emma)</s1></fA11><fA11 i1="49" i2="1"><s1>STRENGMAN (Eric)</s1></fA11><fA11 i1="50" i2="1"><s1>TEUMER (Alexander)</s1></fA11><fA11 i1="51" i2="1"><s1>TRABZUNI (Daniah)</s1></fA11><fA11 i1="52" i2="1"><s1>TURNER (Jessica)</s1></fA11><fA11 i1="53" i2="1"><s1>EIJK (Kristel Van)</s1></fA11><fA11 i1="54" i2="1"><s1>ERP (Theo G.m Van)</s1></fA11><fA11 i1="55" i2="1"><s1>TOL (Marie-Jose Van)</s1></fA11><fA11 i1="56" i2="1"><s1>WITTFELD (Katharina)</s1></fA11><fA11 i1="57" i2="1"><s1>WOLF (Christiane)</s1></fA11><fA11 i1="58" i2="1"><s1>WOUDSTRA (Saskia)</s1></fA11><fA11 i1="59" i2="1"><s1>ALEMAN (Andre)</s1></fA11><fA11 i1="60" i2="1"><s1>ALHUSAINI (Saud)</s1></fA11><fA14 i1="01"><s1>Laboratory of Neuro Imaging, David Geffen School of Medicine, University of California</s1><s2>Los Angeles, California</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>25 aut.</sZ></fA14><fA14 i1="02"><s1>Genetic Epidemiology Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane, Queensland</s2><s3>AUS</s3><sZ>2 aut.</sZ><sZ>24 aut.</sZ></fA14><fA14 i1="03"><s1>Quantitative Genetics Laboratory, Queensland Institute of Medical Research</s1><s2>Brisbane, Queensland</s2><s3>AUS</s3><sZ>2 aut.</sZ></fA14><fA14 i1="04"><s1>Broad Institute of Harvard University and MIT</s1><s2>Cambridge, Massachusetts</s2><s3>USA</s3><sZ>2 aut.</sZ></fA14><fA14 i1="05"><s1>Department of Human Genetics, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ></fA14><fA14 i1="06"><s1>Department of Psychiatry, Radboud University Nijmegen Medical Centre</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ></fA14><fA14 i1="07"><s1>Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen</s1><s2>Nijmegen</s2><s3>NLD</s3><sZ>3 aut.</sZ><sZ>42 aut.</sZ></fA14><fA14 i1="08"><s1>Olin Neuropsychiatry Research Center, Institute of Living, Hartford Hospital</s1><s2>Hartford, Connecticut</s2><s3>USA</s3><sZ>6 aut.</sZ></fA14><fA14 i1="09"><s1>Department of Psychiatry, Yale University School of Medicine</s1><s2>New Haven, Connecticut</s2><s3>USA</s3><sZ>6 aut.</sZ></fA14><fA14 i1="10"><s1>Laboratory of Human Genetics and Cognitive Functions, Institut Pasteur</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></fA14><fA14 i1="11"><s1>Centre Nationale de Recherche Scientifique (CNRS) Unité de Recherche Associee (URA) 2182 Genes, Synapses and Cognition, Institut Pasteur</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></fA14><fA14 i1="12"><s1>Department of Neuroscience, Université Paris Diderot, Sorbonne Paris Cite</s1><s2>Paris</s2><s3>FRA</s3><sZ>7 aut.</sZ></fA14><fA14 i1="13"><s1>Department of Psychiatry and Psychotherapy, University of Greifswald</s1><s2>Greifswald</s2><s3>DEU</s3><sZ>8 aut.</sZ><sZ>56 aut.</sZ></fA14><fA14 i1="14"><s1>Institute of Psychology, Department of Clinical Psychology and Psychotherapy, University of Heidelberg</s1><s2>Heidelberg</s2><s3>DEU</s3><sZ>8 aut.</sZ></fA14><fA14 i1="15"><s1>Department of Psychiatry, Rudolf Magnus Institute, University Medical Center Utrecht</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>9 aut.</sZ></fA14><fA14 i1="16"><s1>Institute of Clinical Medicine, University of Oslo</s1><s2>Oslo</s2><s3>NOR</s3><sZ>10 aut.</sZ><sZ>12 aut.</sZ><sZ>32 aut.</sZ></fA14><fA14 i1="17"><s1>The Hospital for Sick Children, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>11 aut.</sZ></fA14><fA14 i1="18"><s1>Institute of Basic Medical Sciences, Department of Biostatistics, University of Oslo</s1><s2>Oslo</s2><s3>NOR</s3><sZ>12 aut.</sZ></fA14><fA14 i1="19"><s1>Clinical Neuroimaging Laboratory, Department of Anatomy, National University of Ireland Galway</s1><s2>Galway</s2><s3>IRL</s3><sZ>13 aut.</sZ></fA14><fA14 i1="20"><s1>Clinical Neuroimaging Laboratory, Department of Psychiatry, National University of Ireland Galway</s1><s2>Galway</s2><s3>IRL</s3><sZ>22 aut.</sZ></fA14><fA14 i1="21"><s1>Rotman Research Institute, University of Toronto</s1><s2>Toronto, Ontario</s2><s3>CAN</s3><sZ>14 aut.</sZ></fA14><fA14 i1="22"><s1>Dr Einar Martens Research Group for Biological Psychiatry, Department of Clinical Medicine, University of Bergen</s1><s2>Bergen</s2><s3>NOR</s3><sZ>15 aut.</sZ></fA14><fA14 i1="23"><s1>Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital</s1><s2>Bergen</s2><s3>NOR</s3><sZ>15 aut.</sZ></fA14><fA14 i1="24"><s1>Department of Diagnostic Radiology and Neuroradiology, University of Greifswald</s1><s2>Greifswald</s2><s3>DEU</s3><sZ>16 aut.</sZ></fA14><fA14 i1="25"><s1>Central Institute of Mental Health, University of Heidelberg-Medical Faculty Mannheim</s1><s2>Mannheim</s2><s3>DEU</s3><sZ>17 aut.</sZ></fA14><fA20><s1>552-561</s1></fA20><fA21><s1>2012</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>22883</s2><s5>354000507712530120</s5></fA43><fA44><s0>0000</s0><s1>© 2012 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>42 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>12-0224071</s0></fA47><fA60><s1>P</s1><s3>CR</s3></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Nature genetics</s0></fA64><fA66 i1="01"><s0>USA</s0></fA66><fC01 i1="01" l="ENG"><s0>Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease<sup>1,2</sup> and is reduced in schizophrenia<sup>3</sup>, major depression<sup>4</sup> and mesial temporal lobe epilepsy<sup>5</sup>. Whereas many brain imaging phenotypes are highly heritable<sup>6,7</sup>, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10<sup>-16</sup>) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10<sup>-12</sup>). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1 q23.3; N = 6,500; P = 5.81 × 10<sup>-7</sup>).</s0></fC01><fC02 i1="01" i2="X"><s0>002A07</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Identification</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Identification</s0><s5>01</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Identificación</s0><s5>01</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Variant</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Variant</s0><s5>02</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Variante</s0><s5>02</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Homme</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Human</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Hombre</s0><s5>03</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Intracrânien</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Intracranial</s0><s5>04</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Intracraneal</s0><s5>04</s5></fC03><fN21><s1>170</s1></fN21><fN44 i1="01"><s1>OTO</s1></fN44><fN82><s1>OTO</s1></fN82></pA></standard></inist></record>Pour manipuler ce document sous Unix (Dilib)
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