Novel genetic loci associated with hippocampal volume
Derrek P. Hibar(University of Southern California), Hieab H.H. Adams(Erasmus MC), Neda Jahanshad(University of Southern California), Ganesh Chauhan(Université de Bordeaux), Jason L. Stein(University of North Carolina at Chapel Hill), Edith Hofer(Medical University of Graz), Miguel E. Rentería(QIMR Berghofer Medical Research Institute), Joshua C. Bis(University of Washington), Alejandro Arias Vásquez(Radboud University Nijmegen), M. Kamran Ikram(National University of Singapore), Sylvane Desrivières(King's College London), Meike W. Vernooij(Erasmus MC), Lucija Abramovic(Heidelberg University), Saud Alhusaini(Montreal Neurological Institute and Hospital), Najaf Amin(Erasmus MC), Micael Andersson(Sahlgrenska University Hospital), Konstantinos Arfanakis(Rush University Medical Center), Benjamin S. Aribisala(Lagos State University), Nicola J. Armstrong(Murdoch University), Lavinia Athanasiu(Oslo University Hospital), Tomas Axelsson(Uppsala University), Ashley Beecham(University of Miami), Alexa Beiser(Boston University), Manon Bernard(University of Toronto), Susan H. Blanton(University of Miami), Marc M. Bohlken(Heidelberg University), Marco P. Boks(Heidelberg University), Janita Bralten(Radboud University Nijmegen), Adam M. Brickman(Columbia University Irving Medical Center), Owen Carmichael(Pennington Biomedical Research Center), M. Mallar Chakravarty(Douglas Mental Health University Institute), Qiang Chen(Lieber Institute for Brain Development), Christopher R. K. Ching(University of Southern California), Vincent Chouraki(Boston University), Gabriel Cuéllar-Partida(QIMR Berghofer Medical Research Institute), Fabrice Crivello(Centre National de la Recherche Scientifique), Anouk den Braber(Vrije Universiteit Amsterdam), Nhat Trung Doan(University of Oslo), Stefan Ehrlich(Massachusetts General Hospital), Sudheer Giddaluru(University of Oslo), Aaron L. Goldman(Ames National Laboratory), Rebecca F. Gottesman(Johns Hopkins University), O. Grimm(Heidelberg University), Michael Griswold(University of Mississippi Medical Center), Tulio Guadalupe(Max Planck Institute for Psycholinguistics), Boris A. Gutman(University of Southern California), Johanna Haß(Georgia Institute of Technology), Unn K. Haukvik(University of Oslo), David Hoehn(Max Planck Institute of Psychiatry), Avram J. Holmes(Heidelberg University), Martine Hoogman(Radboud University Nijmegen), Deborah Janowitz(Universitätsmedizin Greifswald), Tianye Jia(King's College London), Kjetil Nordbø Jørgensen(University of Oslo), Nazanin Karbalai(Max Planck Institute of Psychiatry), Dalia Kasperavičiūtė(University College London), Sungeun Kim(Indiana University School of Medicine), Marieke Klein(Radboud University Nijmegen), Bernd Kraemer(Heidelberg University), Phil H. Lee(Broad Institute), David C. Liewald(Edinburgh College), Lorna M. Lopez(University of Edinburgh), Michelle Luciano(MedStar Health), Christine Macare(King's College London), André F. Marquand(Radboud University Nijmegen), Mar Matarín(Epilepsy Research UK), Karen A. Mather(UNSW Sydney), Manuel Mattheisen(Aarhus University), David R. McKay(Hartford Hospital), Yuri Milaneschi(Amsterdam Neuroscience), Susana Muñoz Maniega(University of Edinburgh), Kwangsik Nho(Indiana University School of Medicine), Allison C. Nugent(University College Dublin), Paul Nyquist(Johns Hopkins University), Loes M. Olde Loohuis, Jaap Oosterlaan(Amsterdam Neuroscience), Martina Papmeyer(University of Bern), Lukas Pirpamer(Medical University of Graz), Benno Pütz(Max Planck Institute of Psychiatry), Adaikalavan Ramasamy(King's College London), Jennifer S. Richards(Radboud University Nijmegen), Shannon L. Risacher(Indiana University School of Medicine), Roberto Roiz-Santiañez(Universidad de Cantabria), Nanda Rommelse(Radboud University Nijmegen), Stefan Ropele(University of Graz), Emma Rose(Trinity College Dublin), Natalie A. Royle(University of Edinburgh), Tatjana Rundek(University of Miami), Philipp G. Sämann(Max Planck Institute of Psychiatry), Arvin Saremi(University of Southern California), Claudia L. Satizábal(Boston University), Lianne Schmaal(Orygen Youth Health), Andrew J. Schork(University of California System), Li Shen(Wuhan University), Jean Shin(University of Toronto), Elena Shumskaya(Radboud University Nijmegen), Albert V. Smith(University of Iceland), Emma Sprooten(Hartford Hospital), Lachlan T. Strike(The University of Queensland), Alexander Teumer(Universitätsmedizin Greifswald), Diana Tordesillas‐Gutiérrez(Universidad de Cantabria), Roberto Toro(Centre National de la Recherche Scientifique), Daniah Trabzuni(King Faisal Specialist Hospital & Research Centre), Stella Trompet(Leiden University Medical Center), Dhananjay Vaidya(Johns Hopkins University), Jeroen van der Grond(Leiden University Medical Center), Sven J. van der Lee(Erasmus MC), Dennis van der Meer(University Medical Center Groningen), Marjolein M. J. van Donkelaar(Radboud University Nijmegen), Kristel R. van Eijk(Heidelberg University), Theo G.M. van Erp(University of California, Irvine), Daan van Rooij(University Medical Center Groningen), Esther Walton(Georgia State University), Lars T. Westlye(Oslo University Hospital), Christopher D. Whelan(University of Southern California), B. Gwen Windham(University of Oslo), Anderson M. Winkler(University of Mississippi Medical Center), Katharina Wittfeld(Universitätsmedizin Greifswald), Girma Woldehawariat(National Institutes of Health), Christiane Wolf(German Center for Neurodegenerative Diseases), Thomas Wolfers(Radboud University Nijmegen), Lisa R. Yanek(Johns Hopkins University), Jingyun Yang(Rush University Medical Center), Alex Zijdenbos(Rush University Medical Center), Marcel P. Zwiers(Radboud University Nijmegen), Ingrid Agartz(University of Oslo), Laura Almasy(The University of Texas Rio Grande Valley), David Ames(Children's Hospital of Philadelphia), Philippe Amouyel(Inserm), Ole A. Andreassen(Oslo University Hospital), Sampath Arepalli(The University of Melbourne), Amelia A. Assareh(UNSW Sydney), Sandra Barral(Columbia University Irving Medical Center), Mark E. Bastin(Edinburgh College), Diane M. Becker(Johns Hopkins University), James T. Becker(National Institutes of Health), David A. Bennett(Rush University Medical Center), John Blangero(Texas Biomedical Research Institute), Hans van Bokhoven(Radboud University Nijmegen), Dorret I. Boomsma(Vrije Universiteit Amsterdam), Henry Brodaty(University of Pittsburgh), Rachel M. Brouwer(University Medical Center Utrecht), Han G. Brunner(Radboud University Nijmegen), Randy L. Buckner(Maastricht University Medical Centre), Jan K. Buitelaar(Radboud University Nijmegen), Kazima Bulayeva(Harvard University Press), Wiepke Cahn(University Medical Center Utrecht), Vince D. Calhoun(Mind Research Network), Dara M. Cannon(University of New Mexico), Gianpiero L. Cavalleri(Royal College of Surgeons in Ireland), Ching‐Yu Cheng(Northwestern Polytechnical University), Sven Cichon(University of Bonn), Mark Cookson(National Institutes of Health), Aiden Corvin(Trinity College Dublin), Benedicto Crespo‐Facorro(Universidad de Cantabria), Joanne E. Curran(Karolinska Institutet), Michael Czisch(Utrecht University), Anders M. Dale(Forschungszentrum Jülich), Gareth E. Davies(University of California San Diego), Anton J. M. de Craen(Avera Health), Eco J. C. de Geus(Vrije Universiteit Amsterdam), Philip L. De Jager(Broad Institute), Greig I. de Zubicaray(Broad Institute), Ian J. Deary(University of Edinburgh), Stéphanie Debette(Boston University), Charles DeCarli(Université de Bordeaux), Norman Delanty(Royal College of Surgeons in Ireland), Chantal Depondt(Université Libre de Bruxelles), Anita L. DeStefano(Boston University), Allissa Dillman(National Institutes of Health), Srdjan Djurovic(Université Libre de Bruxelles), Gary Donohoe(Oslo University Hospital), Wayne C. Drevets(Trinity College Dublin), Ravi Duggirala(Texas Biomedical Research Institute), Thomas D. Dyer(Texas Biomedical Research Institute), Christian Enzinger(Medical University of Graz), Susanne Erk(Janssen (United States)), Thomas Espeseth(Oslo University Hospital), Iryna O. Fedko(Amsterdam Neuroscience), Guillén Fernández(Radboud University Nijmegen), Luigi Ferrucci(Charité - Universitätsmedizin Berlin), Simon E. Fisher(Radboud University Nijmegen), Debra Fleischman(Rush University Medical Center), Ian Ford(Rush University Medical Center), Myriam Fornage(University of Glasgow), Tatiana M. Foroud(Indiana University – Purdue University Indianapolis), Peter T. Fox(Rensselaer Polytechnic Institute), Clyde Francks(Radboud University Nijmegen), Masaki Fukunaga(Okayama University), J. Raphael Gibbs(The University of Melbourne), David C. Glahn(Hartford Hospital), Randy L. Gollub(Harvard University), Harald H.H. Göring(Karolinska Institutet), Robert C. Green(Harvard University), Oliver Gruber(Heidelberg University), Vilmundur Guðnason(University of Iceland), Sebastian Guelfi(University College London), Asta K. Håberg(Brigham and Women's Hospital), Narelle K. Hansell(The University of Queensland), John Hardy(National Hospital for Neurology and Neurosurgery), Catharina A. Hartman(University Medical Center Groningen), Ryota Hashimoto(St Olav's University Hospital), Katrin Hegenscheid(Universitätsmedizin Greifswald), Andreas Heinz(Janssen (United States)), Stéphanie Le Hellard(University of Oslo), Dena Hernández(The University of Melbourne), Dirk J. Heslenfeld(Universitätsmedizin Greifswald), Beng‐Choon Ho(Vietnam National University Ho Chi Minh City), Pieter J. Hoekstra(University Medical Center Groningen), Wolfgang Hoffmann(Universitätsmedizin Greifswald), Albert Hofman(Harvard University), Florian Holsboer(University of Iowa), Georg Homuth(Harvard University), Norbert Hosten(Universitätsmedizin Greifswald), Jouke‐Jan Hottenga(Vrije Universiteit Amsterdam), Matthew J. Huentelman(HolsboerMaschmeyer NeuroChemie (Germany)), Hilleke E. Hulshoff Pol(University Medical Center Utrecht), Masashi Ikeda(Universitätsmedizin Greifswald), Clifford R. Jack(Translational Genomics Research Institute), Mark Jenkinson(University of Mississippi Medical Center), Robert Johnson(Fujita Health University), Erik G. Jönsson(Stockholm University), J. Wouter Jukema(Leiden University Medical Center), René S. Kahn(University Medical Center Utrecht), Ryota Kanai(University of Maryland, Baltimore), Iwona Kłoszewska(Medical University of Lodz), David S. Knopman(RIKEN Center for Brain Science), Peter Kochunov(University of Maryland, Baltimore), John B. Kwok(University of Maryland, Baltimore), Stephen M. Lawrie(Royal Edinburgh Hospital), Hervé Lemaître(CY Cergy Paris Université), Xinmin Liu(UNSW Sydney), Dan L. Longo(Délégation Paris 5), Oscar L. Lopez(Columbia University Irving Medical Center), Simon Lovestone(University of Pittsburgh), Oliver Martinez(Université de Bordeaux), Jean‐Luc Martinot(Unité de Nutrition Humaine), Venkata S. Mattay(Johns Hopkins University), Colm McDonald(University of New Mexico), Andrew M. McIntosh(Australian National University), Francis J. McMahon(National Human Genome Research Institute), Katie L. McMahon(Johns Hopkins University), Patrizia Mecocci(The University of Queensland), Ingrid Melle(Oslo University Hospital), Andreas Meyer‐Lindenberg(Heidelberg University), Sebastian Mohnke(Janssen (United States)), Grant W. Montgomery(QIMR Berghofer Medical Research Institute), Derek W. Morris(Oslo University Hospital), Thomas H. Mosley(University of Oslo), Thomas W. Mühleisen(University of Bonn), Bertram Müller‐Myhsok(University of Perugia), Michael A. Nalls(National Institutes of Health), Matthias Nauck(University of Liverpool), Thomas E. Nichols(Universitätsmedizin Greifswald), Wiro J. Niessen(Erasmus MC), Markus M. Nöthen(University of Bonn), Lars Nyberg(Umeå University), Kazutaka Ohi(St Olav's University Hospital), Rene L. Olvera(Indiana University School of Medicine), Roel A. Ophoff(University Medical Center Utrecht), Massimo Pandolfo(Université Libre de Bruxelles), Tomáš Paus(University of Bonn), Zdenka Pausová(University of Toronto), Brenda W.J.H. Penninx(Amsterdam Neuroscience), G. Bruce Pike(University of Calgary), Steven G. Potkin(University of California, Irvine), Bruce M. Psaty(University of Calgary), Simone Reppermund(Group Health Cooperative), Marcella Rietschel(Heidelberg University), Joshua L. Roffman(Massachusetts General Hospital), Nina Romanczuk‐Seiferth(Janssen (United States)), Jerome I. Rotter(Cedars-Sinai Medical Center), Mina Ryten(King's College London), Ralph L. Sacco(University of Miami), Perminder S. Sachdev(University of Miami), Andrew J. Saykin(Indiana University School of Medicine), Reinhold Schmidt(Munich University of Applied Sciences), Helena Schmidt(Maastricht University), Peter R. Schofield(University of Maryland, Baltimore), Sigurdur Sigursson(Icelandic Heart Association), Andrew Simmons(King's College London), Andrew Singleton(National Institutes of Health), Sanjay M. Sisodiya(University College London), Colin Smith(King's College London), Jordan W. Smoller(Broad Institute), Hilkka Soininen(University of Eastern Finland), Vidar M. Steen(University of Oslo), David J. Stott(Kuopio University Hospital), Jessika E. Sussmann(Royal Edinburgh Hospital), Anbupalam Thalamuthu(UNSW Sydney), Arthur W. Toga(University of Glasgow), Bryan J. Traynor(The University of Melbourne), Juan C. Troncoso(University of Southern California), Magda Tsolaki(Johns Hopkins University), Christophe Tzourio(Université de Bordeaux), André G. Uitterlinden(Université de Bordeaux), Maria C. Valdés Hernández(University of Edinburgh), Marcel van der Brug(Erasmus University Rotterdam), Aad van der Lugt(Erasmus MC), Nic J.A. van der Wee(Leiden University Medical Center), Neeltje E. M. van Haren(Heidelberg University), Dennis van ‘t Ent, Marie‐José van Tol(Leiden University), Badri N. Vardarajan(Columbia University Irving Medical Center), Bruno Vellas(University Medical Center Groningen), Dick J. Veltman(Amsterdam Neuroscience), Henry Völzke(Universitätsmedizin Greifswald), Henrik Walter(Janssen (United States)), Joanna M. Wardlaw(University of Edinburgh), Thomas H. Wassink(Université Toulouse III - Paul Sabatier), Michael E. Weale(King's College London), D.R. Weinberger(University of Iowa), Michael W. Weiner(Johns Hopkins University), Wei Wen(University of Miami), Eric Westman(San Francisco VA Medical Center), Tonya White(Erasmus MC), Tien Yin Wong(Ollscoil na Gaillimhe – University of Galway), Clinton B. Wright(University of Miami), Ronald H. Zielke(Fujita Health University), Alan B. Zonderman(National Institutes of Health), Nicholas G. Martin(QIMR Berghofer Medical Research Institute), Cornelia M. van Duijn(Erasmus MC), Margaret J. Wright(Johns Hopkins University), W. T. Longstreth(National Institute on Aging), Günter Schumann(King's College London), Hans J. Grabe(Universitätsmedizin Greifswald), Barbara Franke(Radboud University Nijmegen), Lenore J. Launer(University of Washington), Sarah E. Medland(QIMR Berghofer Medical Research Institute), Sudha Seshadri(Boston University), Paul M. Thompson(University of Southern California), M. Arfan Ikram(National University of Singapore)
Cited by 335Open Access
Abstract
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 ( r g =−0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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