Genetic architecture of subcortical brain structures in 38,851 individuals.

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ID: 65540
2019
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Abstract
Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection 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.
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satizabal2019geneticnature Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors 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;Lee, Phil H;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;Buckner, Randy L;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 L;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 C;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 N;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;Smoller, Jordan W;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;
Journal nature genetics
Year 2019
DOI
10.1038/s41588-019-0511-y
URL
Keywords
lebanon knowledge translation hospital managers evidence-based management health management research

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