Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide
Authors: Satizabal Claudia L , Adams Hieab HH , Hibar Derrek P , White Charles C , Stein Jason L , Scholz Markus , Sargurupremraj Murali , Jahanshad Neda , 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 , Renteria Miguel E , Kim Sungeun , Höhn David , Armstrong Nicola J , Chen Qiang , Holmes Avram J , Braber Anouk den , 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 , Karbalai 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 , Knol Maria J , 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 WJH , Calhoun Vince D , Chakravarty M Mallar , Marquand Andre , Macare Christine , Masouleh Shahrzad Kharabian , Oosterlaan Jaap , Amouyel Philippe , Hegenscheid Katrin , Rotter Jerome I , Schork Andrew J , Liewald David CM , De Zubicaray Greig I , Wong Tien Yin , Shen Li , Sämann Philipp G , Brodaty Henry , Roffman Joshua L , De Geus Eco JC , Tsolaki Magda , Erk Susanne , Van Eijk Kristel R , Cavalleri Gianpiero L , Van der Wee Nic JA , 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 GM , Wolf Christiane , Kwok John BJ , Vellas Bruno , Heinz Andreas , Loohuis Loes M Olde , Delanty Norman , Ho Beng-Choon , Ching Christopher RK , Shumskaya Elena , Hofman Albert , Van der Meer Dennis , Homuth Georg , Psaty Bruce M , Bastin Mark , Montgomery Grant W , Foroud Tatiana M , Reppermund Simone , Hottenga Jouke-Jan , Simmons Andrew , Meyer-Lindenberg Andreas , Cahn Wiepke , Whelan Christopher D , Van Donkelaar Marjolein MJ , Yang Qiong , Hosten Norbert , Green Robert C , Thalamuthu Anbupalam , Mohnke Sebastian , Pol Hilleke E Hulshoff , 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 , Smith George Davey , 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 , Smoller Jordan W , Van Tol Marie-Jose , Sussmann Jessika E , Paus Tomas , Lemaître Hervé , Mazoyer Bernard , Andreassen Ole A , Holsboer Florian , 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 EM , 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 A , 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 
Published: August 2017

AbstractSubcortical 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 forDrosophilaorthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.