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    Common genetic variants influence human subcortical brain structures


    Hibar, Derrek P., Stein, Jason L., Renteria, Miguel E., Arias-Vasquez, Alejandro, Desrivières, Sylvane, Jahanshad, Neda, Toro, Roberto, Wittfeld, Katharina, Abramovic, Lucija, Andersson, Micael, Aribisala, Benjamin S., Armstrong, Nicola J., Bernard, Manon, Bohlken, Marc M., Boks, Marco P., Bralten, Janita, Brown, Andrew A., Mallar Chakravarty, M., Chen, Qiang, Ching, Christopher R. K., Cuellar-Partida, Gabriel, den Braber, Anouk, Giddaluru, Sudheer, Goldman, Aaron L., Grimm, Oliver, Guadalupe, Tulio, Hass, Johanna, Woldehawariat, Girma, Holmes, Avram J., Hoogman, Martine, Janowitz, Deborah, Jia, Tianye, Kim, Sungeun, Klein, Marieke, Kraemer, Bernd, Lee, Phil H., Olde Loohuis, Loes M., Luciano, Michelle, Macare, Christine, Mather, Karen A., Mattheisen, Manuel, Milaneschi, Yuri, Nho, Kwangsik, Papmeyer, Martina, Ramasamy, Adaikalavan, Risacher, Shannon L., Roiz-Santiañez, Roberto, Rose, Emma J., Salami, Alireza, Sämann, Philipp G., Schmaal, Lianne, Schork, Andrew J., Shin, Jean, Strike, Lachlan T., Teumer, Alexander, van Donkelaar, Marjolein M. J., van Eijk, Kristel R., Walters, Raymond K., Westlye, Lars T., Whelan, Christopher D., Winkler, Anderson M., Zwiers, Marcel P., Alhusaini, Saud, Athanasiu, Lavinia, Ehrlich, Stefan, Hakobjan, Marina M. H., Hartberg, Cecilie B., Haukvik, Unn K., Heister, Angelien J. G. A. M., Hoehn, David, Kasperaviciute, Dalia, Liewald, David C. M., Lopez, Lorna M., Makkinje, Remco R. R., Matarin, Mar, Naber, Marlies A. M., Reese McKay, D., Needham, Margaret, Nugent, Allison C., Pütz, Benno, Royle, Natalie A., Shen, Li, Sprooten, Emma, Trabzuni, Daniah, van der Marel, Saskia S. L., van Hulzen, Kimm J. E., Walton, Esther, Wolf, Christiane, Almasy, Laura, Ames, David, Arepalli, Sampath, Assareh, Amelia A., Bastin, Mark E., Brodaty, Henry, Bulayeva, Kazima B., Carless, Melanie A., Cichon, Sven, Corvin, Aiden, Curran, Joanne E., Czisch, Michael, de Zubicaray, Greig I., Dillman, Allissa, Duggirala, Ravi, Dyer, Thomas D., Erk, Susanne, Fedko, Iryna O., Ferrucci, Luigi, Foroud, Tatiana M., Fox, Peter T., Fukunaga, Masaki, Raphael Gibbs, J., Göring, Harald H. H., Green, Robert C., Guelfi, Sebastian, Hansell, Narelle K., Hartman, Catharina A., Hegenscheid, Katrin, Heinz, Andreas, Hernandez, Dena G., Heslenfeld, Dirk J., Hoekstra, Pieter J., Holsboer, Florian, Homuth, Georg, Hottenga, Jouke-Jan, Ikeda, Masashi, Jack, Clifford R., Jenkinson, Mark, Johnson, Robert, Kanai, Ryota, Keil, Maria, Kent, Jack W., Kochunov, Peter, Kwok, John B., Lawrie, Stephen M., Liu, Xinmin, Longo, Dan L., McMahon, Katie L., Meisenzahl, Eva, Melle, Ingrid, Mohnke, Sebastian, Montgomery, Grant W., Mostert, Jeanette C., Mühleisen, Thomas W., Nalls, Michael A., Nichols, Thomas E., Nilsson, Lars G., Nöthen, Markus M., Ohi, Kazutaka, Olvera, Rene L., Perez-Iglesias, Rocio, Bruce Pike, G., Potkin, Steven G., Reinvang, Ivar, Reppermund, Simone, Rietschel, Marcella, Romanczuk-Seiferth, Nina, Rosen, Glenn D., Rujescu, Dan, Schnell, Knut, Schofield, Peter R., Smith, Colin, Steen, Vidar M., Sussmann, Jessika E., Thalamuthu, Anbupalam, Toga, Arthur W., Traynor, Bryan J., Troncoso, Juan, Turner, Jessica A., Valdés Hernández, Maria C., van 't Ent, Dennis, van der Brug, Marcel, van der Wee, Nic J. A., van Tol, Marie-Jose, Veltman, Dick J., Wassink, Thomas H., Westman, Eric, Zielke, Ronald H., Zonderman, Alan B., Ashbrook, David G., Hager, Reinmar, Lu, Lu, McMahon, Francis J., Morris, Derek W., Williams, Robert W., Brunner, Han G., Buckner, Randy L., Buitelaar, Jan K., Cahn, Wiepke, Calhoun, Vince D., Cavalleri, Gianpiero L., Crespo-Facorro, Benedicto, Dale, Anders M., Davies, Gareth E., Delanty, Norman, Depondt, Chantal, Djurovic, Srdjan, Drevets, Wayne C., Espeseth, Thomas, Gollub, Randy L., Ho, Beng-Choon, Hoffmann, Wolfgang, Hosten, Norbert, Kahn, René S., Le Hellard, Stephanie, Meyer-Lindenberg, Andreas, Müller-Myhsok, Bertram, Nauck, Matthias, Nyberg, Lars, Pandolfo, Massimo, Penninx, Brenda W. J. H., Roffman, Joshua L., Sisodiya, Sanjay M., Smoller, Jordan W., van Bokhoven, Hans, van Haren, Neeltje E. M., Völzke, Henry, Walter, Henrik, Weiner, Michael W., Wen, Wei, White, Tonya, Agartz, Ingrid, Andreassen, Ole A., Blangero, John, Boomsma, Dorret I., Brouwer, Rachel M., Cannon, Dara M., Cookson, Mark R., de Geus, Eco J. C., Deary, Ian J., Donohoe, Gary, Fernández, Guillén, Fisher, Simon E., Francks, Clyde, Glahn, David C., Grabe, Hans J., Gruber, Oliver, Hardy, John, Hashimoto, Ryota, Hulshoff Pol, Hilleke E., Jönsson, Erik G., Kloszewska, Iwona, Lovestone, Simon, Mattay, Venkata S., Mecocci, Patrizia, McDonald, Colm, McIntosh, Andrew M., Ophoff, Roel A., Paus, Tomas, Pausova, Zdenka, Ryten, Mina, Sachdev, Perminder S., Saykin, Andrew J., Simmons, Andy, Singleton, Andrew, Soininen, Hilkka, Wardlaw, Joanna M., Weale, Michael E., Weinberger, Daniel R., Adams, Hieab H. H., Launer, Lenore J., Seiler, Stephan, Schmidt, Reinhold, Chauhan, Ganesh, Satizabal, Claudia L., Becker, James T., Yanek, Lisa, van der Lee, Sven J., Ebling, Maritza, Fischl, Bruce, Longstreth, W. T., Greve, Douglas, Schmidt, Helena, Nyquist, Paul, Vinke, Louis N., van Duijn, Cornelia M., Xue, Luting, Mazoyer, Bernard, Bis, Joshua C., Gudnason, Vilmundur, Seshadri, Sudha, Ikram, M. Arfan, Martin, Nicholas G., Wright, Margaret J., Schumann, Gunter, Franke, Barbara, 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: 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
    Related URLs:
    URI: https://mural.maynoothuniversity.ie/id/eprint/17224
    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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