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    Common genetic variants influence human subcortical brain structures


    Hibar, Derrek P. and Stein, Jason L. and Renteria, Miguel E. and Arias-Vasquez, Alejandro and Desrivières, Sylvane and Jahanshad, Neda and Toro, Roberto and Wittfeld, Katharina and Abramovic, Lucija and Andersson, Micael and Aribisala, Benjamin S. and Armstrong, Nicola J. and Bernard, Manon and Bohlken, Marc M. and Boks, Marco P. and Bralten, Janita and Brown, Andrew A. and Mallar Chakravarty, M. and Chen, Qiang and Ching, Christopher R. K. and Cuellar-Partida, Gabriel and den Braber, Anouk and Giddaluru, Sudheer and Goldman, Aaron L. and Grimm, Oliver and Guadalupe, Tulio and Hass, Johanna and Woldehawariat, Girma and Holmes, Avram J. and Hoogman, Martine and Janowitz, Deborah and Jia, Tianye and Kim, Sungeun and Klein, Marieke and Kraemer, Bernd and Lee, Phil H. and Olde Loohuis, Loes M. and Luciano, Michelle and Macare, Christine and Mather, Karen A. and Mattheisen, Manuel and Milaneschi, Yuri and Nho, Kwangsik and Papmeyer, Martina and Ramasamy, Adaikalavan and Risacher, Shannon L. and Roiz-Santiañez, Roberto and Rose, Emma J. and Salami, Alireza and Sämann, Philipp G. and Schmaal, Lianne and Schork, Andrew J. and Shin, Jean and Strike, Lachlan T. and Teumer, Alexander and van Donkelaar, Marjolein M. J. and van Eijk, Kristel R. and Walters, Raymond K. and Westlye, Lars T. and Whelan, Christopher D. and Winkler, Anderson M. and Zwiers, Marcel P. and Alhusaini, Saud and Athanasiu, Lavinia and Ehrlich, Stefan and Hakobjan, Marina M. H. and Hartberg, Cecilie B. and Haukvik, Unn K. and Heister, Angelien J. G. A. M. and Hoehn, David and Kasperaviciute, Dalia and Liewald, David C. M. and Lopez, Lorna M. and Makkinje, Remco R. R. and Matarin, Mar and Naber, Marlies A. M. and Reese McKay, D. and Needham, Margaret and Nugent, Allison C. and Pütz, Benno and Royle, Natalie A. and Shen, Li and Sprooten, Emma and Trabzuni, Daniah and van der Marel, Saskia S. L. and van Hulzen, Kimm J. E. and Walton, Esther and Wolf, Christiane and Almasy, Laura and Ames, David and Arepalli, Sampath and Assareh, Amelia A. and Bastin, Mark E. and Brodaty, Henry and Bulayeva, Kazima B. and Carless, Melanie A. and Cichon, Sven and Corvin, Aiden and Curran, Joanne E. and Czisch, Michael and de Zubicaray, Greig I. and Dillman, Allissa and Duggirala, Ravi and Dyer, Thomas D. and Erk, Susanne and Fedko, Iryna O. and Ferrucci, Luigi and Foroud, Tatiana M. and Fox, Peter T. and Fukunaga, Masaki and Raphael Gibbs, J. and Göring, Harald H. H. and Green, Robert C. and Guelfi, Sebastian and Hansell, Narelle K. and Hartman, Catharina A. and Hegenscheid, Katrin and Heinz, Andreas and Hernandez, Dena G. and Heslenfeld, Dirk J. and Hoekstra, Pieter J. and Holsboer, Florian and Homuth, Georg and Hottenga, Jouke-Jan and Ikeda, Masashi and Jack, Clifford R. and Jenkinson, Mark and Johnson, Robert and Kanai, Ryota and Keil, Maria and Kent, Jack W. and Kochunov, Peter and Kwok, John B. and Lawrie, Stephen M. and Liu, Xinmin and Longo, Dan L. and McMahon, Katie L. and Meisenzahl, Eva and Melle, Ingrid and Mohnke, Sebastian and Montgomery, Grant W. and Mostert, Jeanette C. and Mühleisen, Thomas W. and Nalls, Michael A. and Nichols, Thomas E. and Nilsson, Lars G. and Nöthen, Markus M. and Ohi, Kazutaka and Olvera, Rene L. and Perez-Iglesias, Rocio and Bruce Pike, G. and Potkin, Steven G. and Reinvang, Ivar and Reppermund, Simone and Rietschel, Marcella and Romanczuk-Seiferth, Nina and Rosen, Glenn D. and Rujescu, Dan and Schnell, Knut and Schofield, Peter R. and Smith, Colin and Steen, Vidar M. and Sussmann, Jessika E. and Thalamuthu, Anbupalam and Toga, Arthur W. and Traynor, Bryan J. and Troncoso, Juan and Turner, Jessica A. and Valdés Hernández, Maria C. and van 't Ent, Dennis and van der Brug, Marcel and van der Wee, Nic J. A. and van Tol, Marie-Jose and Veltman, Dick J. and Wassink, Thomas H. and Westman, Eric and Zielke, Ronald H. and Zonderman, Alan B. and Ashbrook, David G. and Hager, Reinmar and Lu, Lu and McMahon, Francis J. and Morris, Derek W. and Williams, Robert W. and Brunner, Han G. and Buckner, Randy L. and Buitelaar, Jan K. and Cahn, Wiepke and Calhoun, Vince D. and Cavalleri, Gianpiero L. and Crespo-Facorro, Benedicto and Dale, Anders M. and Davies, Gareth E. and Delanty, Norman and Depondt, Chantal and Djurovic, Srdjan and Drevets, Wayne C. and Espeseth, Thomas and Gollub, Randy L. and Ho, Beng-Choon and Hoffmann, Wolfgang and Hosten, Norbert and Kahn, René S. and Le Hellard, Stephanie and Meyer-Lindenberg, Andreas and Müller-Myhsok, Bertram and Nauck, Matthias and Nyberg, Lars and Pandolfo, Massimo and Penninx, Brenda W. J. H. and Roffman, Joshua L. and Sisodiya, Sanjay M. and Smoller, Jordan W. and van Bokhoven, Hans and van Haren, Neeltje E. M. and Völzke, Henry and Walter, Henrik and Weiner, Michael W. and Wen, Wei and White, Tonya and Agartz, Ingrid and Andreassen, Ole A. and Blangero, John and Boomsma, Dorret I. and Brouwer, Rachel M. and Cannon, Dara M. and Cookson, Mark R. and de Geus, Eco J. C. and Deary, Ian J. and Donohoe, Gary and Fernández, Guillén and Fisher, Simon E. and Francks, Clyde and Glahn, David C. and Grabe, Hans J. and Gruber, Oliver and Hardy, John and Hashimoto, Ryota and Hulshoff Pol, Hilleke E. and Jönsson, Erik G. and Kloszewska, Iwona and Lovestone, Simon and Mattay, Venkata S. and Mecocci, Patrizia and McDonald, Colm and McIntosh, Andrew M. and Ophoff, Roel A. and Paus, Tomas and Pausova, Zdenka and Ryten, Mina and Sachdev, Perminder S. and Saykin, Andrew J. and Simmons, Andy and Singleton, Andrew and Soininen, Hilkka and Wardlaw, Joanna M. and Weale, Michael E. and Weinberger, Daniel R. and Adams, Hieab H. H. and Launer, Lenore J. and Seiler, Stephan and Schmidt, Reinhold and Chauhan, Ganesh and Satizabal, Claudia L. and Becker, James T. and Yanek, Lisa and van der Lee, Sven J. and Ebling, Maritza and Fischl, Bruce and Longstreth, W. T. and Greve, Douglas and Schmidt, Helena and Nyquist, Paul and Vinke, Louis N. and van Duijn, Cornelia M. and Xue, Luting and Mazoyer, Bernard and Bis, Joshua C. and Gudnason, Vilmundur and Seshadri, Sudha and Ikram, M. Arfan and Martin, Nicholas G. and Wright, Margaret J. and Schumann, Gunter and Franke, Barbara and Thompson, Paul M. and Medland, Sarah E. (2015) Common genetic variants influence human subcortical brain structures. Nature Communications, 520 (7546). pp. 224-229. ISSN 2041-1723

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    Abstract

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10−33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability in human brain development, and may help to determine mechanisms of neuropsychiatric dysfunction.

    Item Type: Article
    Keywords: Common genetic variants; influence; human; subcortical; brain structures;
    Academic Unit: Faculty of Science and Engineering > Biology
    Faculty of Science and Engineering > Research Institutes > Human Health Institute
    Item ID: 17224
    Identification Number: https://doi.org/10.1038/nature14101
    Depositing User: Lorna Lopez
    Date Deposited: 24 May 2023 10:59
    Journal or Publication Title: Nature Communications
    Publisher: Nature Publshing Group
    Refereed: Yes
    URI:
    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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