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    Novel genetic loci associated with hippocampal volume

    Hibar, Derrek P. and Adams, Hieab H. H. and Jahanshad, Neda and Chauhan, Ganesh and Stein, Jason L. and Hofer, Edith and Renteria, Miguel E. and Bis, Joshua C. and Arias-Vasquez, Alejandro and Ikram, M. Kamran and Desrivières, Sylvane and Vernooij, Meike W. and Abramovic, Lucija and Alhusaini, Saud and Amin, Najaf and Andersson, Micael and Arfanakis, Konstantinos and Aribisala, Benjamin S. and Armstrong, Nicola J. and Athanasiu, Lavinia and Axelsson, Tomas and Beecham, Ashley H. and Beiser, Alexa and Bernard, Manon and Blanton, Susan H. and Bohlken, Marc M. and Boks, Marco P. and Bralten, Janita and Brickman, Adam M. and Carmichael, Owen and Chakravarty, M. Mallar and Chen, Qiang and Ching, Christopher R. K. and Chouraki, Vincent and Cuellar-Partida, Gabriel and Crivello, Fabrice and Den Braber, Anouk and Doan, Nhat Trung and Ehrlich, Stefan and Giddaluru, Sudheer and Goldman, Aaron L. and Gottesman, Rebecca F. and Grimm, Oliver and Griswold, Michael E. and Guadalupe, Tulio and Gutman, Boris A. and Hass, Johanna and Haukvik, Unn K. and Hoehn, David and Holmes, Avram J. and Hoogman, Martine and Janowitz, Deborah and Jia, Tianye and Jørgensen, Kjetil N. and Karbalai, Nazanin and Kasperaviciute, Dalia and Kim, Sungeun and Klein, Marieke and Kraemer, Bernd and Lee, Phil H. and Liewald, David C. M. and Lopez, Lorna M. and Luciano, Michelle and Macare, Christine and Marquand, Andre F. and Matarin, Mar and Mather, Karen A. and Mattheisen, Manuel and McKay, David R. and Milaneschi, Yuri and Muñoz Maniega, Susana and Nho, Kwangsik and Nugent, Allison C. and Nyquist, Paul and Loohuis, Loes M. Olde and Oosterlaan, Jaap and Papmeyer, Martina and Pirpamer, Lukas and Pütz, Benno and Ramasamy, Adaikalavan and Richards, Jennifer S. and Risacher, Shannon L. and Roiz-Santiañez, Roberto and Rommelse, Nanda and Ropele, Stefan and Rose, Emma J. and Royle, Natalie A. and Rundek, Tatjana and Sämann, Philipp G. and Saremi, Arvin and Satizabal, Claudia L. and Schmaal, Lianne and Schork, Andrew J. and Shen, Li and Shin, Jean and Shumskaya, Elena and Smith, Albert V. and Sprooten, Emma and Strike, Lachlan T. and Teumer, Alexander and Tordesillas-Gutierrez, Diana and Toro, Roberto and Trabzuni, Daniah and Trompet, Stella and Vaidya, Dhananjay and Van der Grond, Jeroen and Van der Lee, Sven J. and Van der Meer, Dennis and Van Donkelaar, Marjolein M. J. and Van Eijk, Kristel R. and Van Erp, Theo G. M. and Van Rooij, Daan and Walton, Esther and Westlye, Lars T. and Whelan, Christopher D. and Windham, Beverly G. and Winkler, Anderson M. and Wittfeld, Katharina and Woldehawariat, Girma and Wolf, Christiane and Wolfers, Thomas and Yanek, Lisa R. and Yang, Jingyun and Zijdenbos, Alex and Zwiers, Marcel P. and Agartz, Ingrid and Almasy, Laura and Ames, David and Amouyel, Philippe and Andreassen, Ole A. and Arepalli, Sampath and Assareh, Amelia A. and Barral, Sandra and Bastin, Mark E. and Becker, Diane M. and Becker, James T. and Bennett, David A. and Blangero, John and van Bokhoven, Hans and Boomsma, Dorret I. and Brodaty, Henry and Brouwer, Rachel M. and Brunner, Han G. and Buckner, Randy L. and Buitelaar, Jan K. and Bulayeva, Kazima B. and Cahn, Wiepke and Calhoun, Vince D. and Cannon, Dara M. and Cavalleri, Gianpiero L. and Cheng, Ching-Yu and Cichon, Sven and Cookson, Mark R. and Corvin, Aiden and Crespo-Facorro, Benedicto and Curran, Joanne E. and Czisch, Michael and Dale, Anders M. and Davies, Gareth E. and De Craen, Anton J. M. and De Geus, Eco J. C. and De Jager, Philip L. and De Zubicaray, Greig I. and Deary, Ian J. and Debette, Stéphanie and DeCarli, Charles and Delanty, Norman and Depondt, Chantal and DeStefano, Anita and Dillman, Allissa and Djurovic, Srdjan and Donohoe, Gary and Drevets, Wayne C. and Duggirala, Ravi and Dyer, Thomas D. and Enzinger, Christian and Erk, Susanne and Espeseth, Thomas and Fedko, Iryna O. and Fernández, Guillén and Ferrucci, Luigi and Fisher, Simon E. and Fleischman, Debra A. and Ford, Ian and Fornage, Myriam and Foroud, Tatiana M. and Fox, Peter T. and Francks, Clyde and Fukunaga, Masaki and Gibbs, J. Raphael and Glahn, David C. and Gollub, Randy L. and Göring, Harald H. H. and Green, Robert C. and Gruber, Oliver and Gudnason, Vilmundur and Guelfi, Sebastian and Håberg, Asta K. and Hansell, Narelle K. and Hardy, John and Hartman, Catharina A. and Hashimoto, Ryota and Hegenscheid, Katrin and Heinz, Andreas and Le Hellard, Stephanie and Hernandez, Dena G. and Heslenfeld, Dirk J. and Ho, Beng-Choon and Hoekstra, Pieter J. and Hoffmann, Wolfgang and Hofman, Albert and Holsboer, Florian and Homuth, Georg and Hosten, Norbert and Hottenga, Jouke-Jan and Huentelman, Matthew and Hulshoff Pol, Hilleke E. and Ikeda, Masashi and Jack Jr, Clifford R. and Jenkinson, Mark and Johnson, Robert and Jönsson, Erik G. and Jukema, J. Wouter and Kahn, René S. and Kanai, Ryota and Kloszewska, Iwona and Knopman, David S. and Kochunov, Peter and Kwok, John B. and Lawrie, Stephen M. and Lemaître, Hervé and Liu, Xinmin and Longo, Dan L. and Lopez, Oscar L. and Lovestone, Simon and Martinez, Oliver and Martinot, Jean-Luc and Mattay, Venkata S. and McDonald, Colm and McIntosh, Andrew M. and McMahon, Francis J. and McMahon, Katie L. and Mecocci, Patrizia and Melle, Ingrid and Meyer-Lindenberg, Andreas and Mohnke, Sebastian and Montgomery, Grant W. and Morris, Derek W. and Mosley, Thomas H. and Mühleisen, Thomas W. and Müller-Myhsok, Bertram and Nalls, Michael A. and Nauck, Matthias and Nichols, Thomas E. and Niessen, Wiro J. and Nöthen, Markus M. and Nyberg, Lars and Ohi, Kazutaka and Olvera, Rene L. and Ophoff, Roel A. and Pandolfo, Massimo and Paus, Tomas and Pausova, Zdenka and Penninx, Brenda W. J. H. and Pike, G. Bruce and Potkin, Steven G. and Psaty, Bruce M. and Reppermund, Simone and Rietschel, Marcella and Roffman, Joshua L. and Romanczuk-Seiferth, Nina and Rotter, Jerome I. and Ryten, Mina and Sacco, Ralph L. and Sachdev, Perminder S. and Saykin, Andrew J. and Schmidt, Reinhold and Schmidt, Helena and Schofield, Peter R. and Sigursson, Sigurdur and Simmons, Andrew and Singleton, Andrew and Sisodiya, Sanjay M. and Smith, Colin and Smoller, Jordan W. and Soininen, Hilkka and Steen, Vidar M. and Stott, David J. and Sussmann, Jessika E. and Thalamuthu, Anbupalam and Toga, Arthur W. and Traynor, Bryan J. and Troncoso, Juan and Tsolaki, Magda and Tzourio, Christophe and Uitterlinden, Andre G. and Hernández, Maria C. Valdés and Van der Brug, Marcel and van der Lugt, Aad and van der Wee, Nic J. A. and Van Haren, Neeltje E. M. and van ’t Ent, Dennis and Van Tol, Marie-Jose and Vardarajan, Badri N. and Vellas, Bruno and Veltman, Dick J. and Völzke, Henry and Walter, Henrik and Wardlaw, Joanna M. and Wassink, Thomas H. and Weale, Michael E. and Weinberger, Daniel R. and Weiner, Michael W. and Wen, Wei and Westman, Eric and White, Tonya and Wong, Tien Y. and Wright, Clinton B. and Zielke, Ronald H. and Zonderman, Alan B. and Martin, Nicholas G. and Van Duijn, Cornelia M. and Wright, Margaret J. and Longstreth, W. T. and Schumann, Gunter and Grabe, Hans J. and Franke, Barbara and Launer, Lenore J. and Medland, Sarah E. and Seshadri, Sudha and Thompson, Paul M. and Ikram, M. Arfan (2017) Novel genetic loci associated with hippocampal volume. Nature Communications, 8 (1). pp. 1-12. ISSN 2041-1723

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    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.

    Item Type: Article
    Keywords: Novel; genetic; loci associated; hippocampal volume;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17195
    Identification Number:
    Depositing User: Lorna Lopez
    Date Deposited: 17 May 2023 10:00
    Journal or Publication Title: Nature Communications
    Publisher: Nature Research
    Refereed: Yes
    Use Licence: This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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