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Lee, Philip

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Lee, Philip

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    Genetic architecture of subcortical brain structures in 38,851 individuals
    (Springer Science and Business Media LLC, 2019-10-21) Satizabal, Claudia L.; Adams, Hieab H. H.; Hibar, Derrek P.; White, Charles C.; Knol, Maria J.; Stein, Jason L.; Scholz, Markus; Sargurupremraj, Muralidharan; Jahanshad, Neda; Roshchupkin, Gennady V.; Smith, Albert V.; Bis, Joshua C.; Jian, Xueqiu; Luciano, Michelle; Hofer, Edith; Teumer, Alexander; van der Lee, Sven J.; Yang, Jingyun; Yanek, Lisa R.; Lee, Tom V.; Li, Shuo; Hu, Yanhui; Koh, Jia Yu; Eicher, John D.; Desrivières, Sylvane; Arias-Vasquez, Alejandro; Chauhan, Ganesh; Athanasiu, Lavinia; Rentería, Miguel E.; Kim, Sungeun; Hoehn, David; Armstrong, Nicola J.; Chen, Qiang; Holmes, Avram J.; den Braber, Anouk; Kloszewska, Iwona; Andersson, Micael; Espeseth, Thomas; Grimm, Oliver; Abramovic, Lucija; Alhusaini, Saud; Milaneschi, Yuri; Papmeyer, Martina; Axelsson, Tomas; Ehrlich, Stefan; Roiz-Santiañez, Roberto; Kraemer, Bernd; Håberg, Asta K.; Jones, Hannah J.; Pike, G. Bruce; Stein, Dan J.; Stevens, Allison; Bralten, Janita; Vernooij, Meike W.; Harris, Tamara B.; Filippi, Irina; Witte, A. Veronica; Guadalupe, Tulio; Wittfeld, Katharina; Mosley, Thomas H.; Becker, James T.; Doan, Nhat Trung; Hagenaars, Saskia P.; Saba, Yasaman; Cuellar-Partida, Gabriel; Amin, Najaf; Hilal, Saima; Nho, Kwangsik; Mirza-Schreiber, Nazanin; Arfanakis, Konstantinos; Becker, Diane M.; Ames, David; Goldman, Aaron L.; Boomsma, Dorret I.; Lovestone, Simon; Giddaluru, Sudheer; Le Hellard, Stephanie; Mattheisen, Manuel; Bohlken, Marc M.; Kasperaviciute, Dalia; Schmaal, Lianne; Lawrie, Stephen M.; Agartz, Ingrid; Walton, Esther; Tordesillas-Gutierrez, Diana; Davies, Gareth E.; Shin, Jean; Ipser, Jonathan C.; Vinke, Louis N.; Hoogman, Martine; Jia, Tianye; Burkhardt, Ralph; Klein, Marieke; Crivello, Fabrice; Janowitz, Deborah; Carmichael, Owen; Haukvik, Unn K.; Aribisala, Benjamin S.; Schmidt, Helena; Strike, Lachlan T.; Cheng, Ching-Yu; Risacher, Shannon L.; Pütz, Benno; Fleischman, Debra A.; Assareh, Amelia A.; Mattay, Venkata S.; Mecocci, Patrizia; Dale, Anders M.; Cichon, Sven; Boks, Marco P.; Matarin, Mar; Penninx, Brenda W. J. H.; Calhoun, Vince D.; Chakravarty, M. Mallar; Marquand, Andre F.; Macare, Christine; Kharabian Masouleh, Shahrzad; Oosterlaan, Jaap; Amouyel, Philippe; Hegenscheid, Katrin; Rotter, Jerome I.; Schork, Andrew J.; Liewald, David C. M.; de Zubicaray, Greig I.; Wong, Tien Yin; Shen, Li; Sämann, Philipp G.; Brodaty, Henry; Roffman, Joshua L.; de Geus, Eco J. C.; Tsolaki, Magda; Erk, Susanne; van Eijk, Kristel R.; Cavalleri, Gianpiero L.; van der Wee, Nic J. A.; McIntosh, Andrew M.; Gollub, Randy; Bulayeva, Kazima B.; Bernard, Manon; Richards, Jennifer S.; Himali, Jayandra J.; Loeffler, Markus; Rommelse, Nanda; Hoffmann, Wolfgang; Westlye, Lars T.; Valdés Hernández, Maria C.; Hansell, Narelle K.; van Erp, Theo G. M.; Wolf, Christiane; Kwok, John B. J.; Vellas, Bruno; Heinz, Andreas; Olde Loohuis, Loes M.; Delanty, Norman; Ho, Beng-Choon; Ching, Christopher R. K.; Shumskaya, Elena; Singh, Baljeet; Hofman, Albert; van der Meer, Dennis; Homuth, Georg; Psaty, Bruce M.; Bastin, Mark E.; Montgomery, Grant W.; Foroud, Tatiana M.; Reppermund, Simone; Hottenga, Jouke-Jan; Simmons, Andrew; Meyer-Lindenberg, Andreas; Cahn, Wiepke; Whelan, Christopher D.; van Donkelaar, Marjolein M. J.; Yang, Qiong; Hosten, Norbert; Green, Robert; Thalamuthu, Anbupalam; Mohnke, Sebastian; Hulshoff Pol, Hilleke E.; Lin, Honghuang; Jack, Clifford R.; Schofield, Peter R.; Mühleisen, Thomas W.; Maillard, Pauline; Potkin, Steven G.; Wen, Wei; Fletcher, Evan; Toga, Arthur W.; Gruber, Oliver; Huentelman, Matthew; Davey Smith, George; Launer, Lenore J.; Nyberg, Lars; Jönsson, Erik G.; Crespo-Facorro, Benedicto; Koen, Nastassja; Greve, Douglas; Uitterlinden, André G.; Weinberger, Daniel R.; Steen, Vidar M.; Fedko, Iryna O.; Groenewold, Nynke A.; Niessen, Wiro J.; Toro, Roberto; Tzourio, Christophe; Longstreth, William T.; Ikram, M. Kamran; van Tol, Marie-Jose; Sussmann, Jessika E.; Paus, Tomas; Lemaître, Hervé; Schroeter, Matthias L.; Mazoyer, Bernard; Andreassen, Ole A.; Holsboer, Florian; Depondt, Chantal; Veltman, Dick J.; Turner, Jessica A.; Pausova, Zdenka; Schumann, Gunter; van Rooij, Daan; Djurovic, Srdjan; Deary, Ian J.; McMahon, Katie L.; Müller-Myhsok, Bertram; Brouwer, Rachel M.; Soininen, Hilkka; Pandolfo, Massimo; Wassink, Thomas H.; Cheung, Joshua W.; Wolfers, Thomas; Martinot, Jean-Luc; Zwiers, Marcel P.; Nauck, Matthias; Melle, Ingrid; Martin, Nicholas G.; Kanai, Ryota; Westman, Eric; Kahn, René S.; Sisodiya, Sanjay M.; White, Tonya; Saremi, Arvin; van Bokhoven, Hans; Brunner, Han G.; Völzke, Henry; Wright, Margaret J.; van ‘t Ent, Dennis; Nöthen, Markus M.; Ophoff, Roel A.; Buitelaar, Jan K.; Fernández, Guillén; Sachdev, Perminder S.; Rietschel, Marcella; van Haren, Neeltje E. M.; Fisher, Simon E.; Beiser, Alexa S.; Francks, Clyde; Saykin, Andrew J.; Mather, Karen A.; Romanczuk-Seiferth, Nina; Hartman, Catharina A.; DeStefano, Anita L.; Heslenfeld, Dirk J.; Weiner, Michael W.; Walter, Henrik; Hoekstra, Pieter J.; Nyquist, Paul A.; Franke, Barbara; Bennett, David A.; Grabe, Hans J.; Johnson, Andrew D.; Chen, Christopher; van Duijn, Cornelia M.; Lopez, Oscar L.; Fornage, Myriam; Wardlaw, Joanna M.; Schmidt, Reinhold; DeCarli, Charles; De Jager, Philip L.; Villringer, Arno; Debette, Stéphanie; Gudnason, Vilmundur; Medland, Sarah E.; Shulman, Joshua M.; Thompson, Paul M.; Seshadri, Sudha; Ikram, M. Arfan; Lee, Philip; Smoller, Jordan; Buckner, Randy
    Subcortical brain structures are integral to motion, consciousness, emotions, and learning. We identified common genetic variation related to the volumes of nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen, and thalamus, using genome-wide association analyses in over 40,000 individuals from CHARGE, ENIGMA and the UK-Biobank. We show that variability in subcortical volumes is heritable, and identify 25 significantly associated loci (20 novel). Annotation of these loci utilizing gene expression, methylation, and neuropathological data identified 62 candidate genes implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.