Novel genetic loci associated with hippocampal volume View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-18

AUTHORS

Derrek P. Hibar, Hieab H. H. Adams, Neda Jahanshad, Ganesh Chauhan, Jason L. Stein, Edith Hofer, Miguel E. Renteria, Joshua C. Bis, Alejandro Arias-Vasquez, M. Kamran Ikram, Sylvane Desrivières, Meike W. Vernooij, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Ashley H. Beecham, Alexa Beiser, Manon Bernard, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Vincent Chouraki, Gabriel Cuellar-Partida, Fabrice Crivello, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, Oliver Grimm, Michael E. Griswold, Tulio Guadalupe, Boris A. Gutman, Johanna Hass, Unn K. Haukvik, David Hoehn, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Kjetil N. Jørgensen, Nazanin Karbalai, Dalia Kasperaviciute, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, David C. M. Liewald, Lorna M. Lopez, Michelle Luciano, Christine Macare, Andre F. Marquand, Mar Matarin, Karen A. Mather, Manuel Mattheisen, David R. McKay, Yuri Milaneschi, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Paul Nyquist, Loes M. Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Lukas Pirpamer, Benno Pütz, Adaikalavan Ramasamy, Jennifer S. Richards, Shannon L. Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Stefan Ropele, Emma J. Rose, Natalie A. Royle, Tatjana Rundek, Philipp G. Sämann, Arvin Saremi, Claudia L. Satizabal, Lianne Schmaal, Andrew J. Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V. Smith, Emma Sprooten, Lachlan T. Strike, Alexander Teumer, Diana Tordesillas-Gutierrez, Roberto Toro, Daniah Trabzuni, Stella Trompet, Dhananjay Vaidya, Jeroen Van der Grond, Sven J. Van der Lee, Dennis Van der Meer, Marjolein M. J. Van Donkelaar, Kristel R. Van Eijk, Theo G. M. Van Erp, Daan Van Rooij, Esther Walton, Lars T. Westlye, Christopher D. Whelan, Beverly G. Windham, Anderson M. Winkler, Katharina Wittfeld, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Lisa R. Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P. Zwiers, Ingrid Agartz, Laura Almasy, David Ames, Philippe Amouyel, Ole A. Andreassen, Sampath Arepalli, Amelia A. Assareh, Sandra Barral, Mark E. Bastin, Diane M. Becker, James T. Becker, David A. Bennett, John Blangero, Hans van Bokhoven, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Kazima B. Bulayeva, Wiepke Cahn, Vince D. Calhoun, Dara M. Cannon, Gianpiero L. Cavalleri, Ching-Yu Cheng, Sven Cichon, Mark R. Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Anton J. M. De Craen, Eco J. C. De Geus, Philip L. De Jager, Greig I. De Zubicaray, Ian J. Deary, Stéphanie Debette, Charles DeCarli, Norman Delanty, Chantal Depondt, Anita DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Christian Enzinger, Susanne Erk, Thomas Espeseth, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra A. Fleischman, Ian Ford, Myriam Fornage, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H. H. Göring, Robert C. Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Asta K. Håberg, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G. Hernandez, Dirk J. Heslenfeld, Beng-Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Matthew Huentelman, Hilleke E. Hulshoff Pol, Masashi Ikeda, Clifford R. Jack, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kloszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Francis J. McMahon, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Steven G. Potkin, Bruce M. Psaty, Simone Reppermund, Marcella Rietschel, Joshua L. Roffman, Nina Romanczuk-Seiferth, Jerome I. Rotter, Mina Ryten, Ralph L. Sacco, Perminder S. Sachdev, Andrew J. Saykin, Reinhold Schmidt, Helena Schmidt, Peter R. Schofield, Sigurdur Sigursson, Andrew Simmons, Andrew Singleton, Sanjay M. Sisodiya, Colin Smith, Jordan W. Smoller, Hilkka Soininen, Vidar M. Steen, David J. Stott, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Magda Tsolaki, Christophe Tzourio, Andre G. Uitterlinden, Maria C. Valdés Hernández, Marcel Van der Brug, Aad van der Lugt, Nic J. A. van der Wee, Neeltje E. M. Van Haren, Dennis van ’t Ent, Marie-Jose Van Tol, Badri N. Vardarajan, Bruno Vellas, Dick J. Veltman, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Thomas H. Wassink, Michael E. Weale, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y. Wong, Clinton B. Wright, Ronald H. Zielke, Alan B. Zonderman, Nicholas G. Martin, Cornelia M. Van Duijn, Margaret J. Wright, W. T. Longstreth, Gunter Schumann, Hans J. Grabe, Barbara Franke, Lenore J. Launer, Sarah E. Medland, Sudha Seshadri, Paul M. Thompson, M. Arfan Ikram

ABSTRACT

The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (rg=-0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness. More... »

PAGES

13624

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  • Journal

    TITLE

    Nature Communications

    ISSUE

    N/A

    VOLUME

    8

    Author Affiliations

  • University of Southern California
  • Erasmus University Medical Center
  • University of Bordeaux
  • University of North Carolina System
  • Medical University of Graz
  • QIMR Berghofer Medical Research Institute
  • University of Washington
  • Radboud University Nijmegen
  • National University of Singapore
  • King's College London
  • University Medical Center Utrecht
  • Royal College of Surgeons in Ireland
  • Umeå University
  • Rush University Medical Center
  • University of Edinburgh
  • Murdoch University
  • Oslo University Hospital
  • Uppsala University
  • University of Miami
  • Boston University
  • University of Toronto
  • Pennington Biomedical Research Center
  • McGill University
  • Lieber Institute for Brain Development
  • University of California Los Angeles
  • Boston University School of Medicine
  • Amsterdam Neuroscience
  • Massachusetts General Hospital
  • Haukeland University Hospital
  • Johns Hopkins University
  • Central Institute of Mental Health
  • University of Mississippi Medical Center
  • Max Planck Institute for Psycholinguistics
  • TU Dresden
  • Diakonhjemmet Hospital
  • Max Planck Institute of Psychiatry
  • Yale University
  • University of Greifswald
  • Imperial College London
  • Indiana University – Purdue University Indianapolis
  • Heidelberg University
  • Broad Institute
  • University College London
  • UNSW Australia
  • Aarhus University
  • National Institute of Mental Health
  • VU University Amsterdam
  • University of Bern
  • University of Oxford
  • Marqués de Valdecilla University Hospital
  • Trinity College Dublin
  • University of California, San Diego
  • University of Iceland
  • Icahn School of Medicine at Mount Sinai
  • University of Queensland
  • Instituto de Investigación Marqués de Valdecilla
  • Institut Pasteur
  • King Faisal Specialist Hospital & Research Centre
  • Leiden University Medical Center
  • University Medical Center Groningen
  • University of California, Irvine
  • Georgia State University
  • University of Würzburg
  • University of Pennsylvania
  • Royal Melbourne Hospital
  • University of Melbourne
  • National Institutes of Health
  • Karolinska Institute
  • University of Pittsburgh
  • Maastricht University Medical Centre
  • Harvard University
  • Mind Research Network
  • University of New Mexico
  • National University of Ireland, Galway
  • University of Bonn
  • Queensland University of Technology
  • Centre Hospitalier Universitaire de Bordeaux
  • University of California, Davis
  • Beaumont Hospital
  • University of Bergen
  • Janssen (United States)
  • Charité
  • National Institute on Aging
  • University of Glasgow
  • The University of Texas Health Science Center at Houston
  • The University of Texas Health Science Center at San Antonio
  • National Institute for Physiological Sciences
  • Norwegian University of Science and Technology
  • Osaka University
  • German Center for Neurodegenerative Diseases
  • University of Iowa
  • HolsboerMaschmeyer NeuroChemie (Germany)
  • Translational Genomics Research Institute
  • Fujita Health University
  • University of Sussex
  • Medical University of Lodz
  • University of Maryland, Baltimore
  • Neuroscience Research Australia
  • Paris Descartes University
  • Columbia University Medical Center
  • Munich Cluster for Systems Neurology
  • German Centre for Cardiovascular Research
  • University of Warwick
  • Delft University of Technology
  • St Olav's University Hospital
  • Child Mind Institute
  • University of Calgary
  • Harbor–UCLA Medical Center
  • Prince of Wales Hospital
  • Icelandic Heart Association
  • University of Eastern Finland
  • Kuopio University Hospital
  • Aristotle University of Thessaloniki
  • Roche (United States)
  • University of Toulouse
  • Sophia Children's Hospital
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ncomms13624

    DOI

    http://dx.doi.org/10.1038/ncomms13624

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1009071788

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28098162


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