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Genetic Architecture of Subcortical Brain Structures in Over 40,000 Individuals Worldwide
Authors :
Arvin Saremi Tomas Axelsson Kristel R. van Eijk Tonya White Elena Shumskaya Christine Macare Christopher Chen Neeltje E.M. van Haren K Hegenscheid Ingrid Melle Benjamin S. Aribisala Clyde Francks Lisa R. Yanek Konstantinos Arfanakis Lars Nyberg Nina Romanczuk-Seiferth Clifford R. Jack Thomas H. Wassink Norman Delanty Oscar L. Lopez Jennifer S. Richards Philippe Amouyel William T. Longstreth Michael W. Weiner Maria J. Knol Ralph Burkhardt Ching-Yu Cheng Wolfgang Hoffmann Norbert Hosten Alexander Teumer Simone Reppermund Markus M. Nöthen Tien Yin Wong Maria del C. Valdés Hernández Bernd Kraemer Murali Sargurupremraj Amelia A. Assareh Jessika E. Sussmann Gabriel Cuellar-Partida Ian J. Deary Ganesh Chauhan Christopher R.K. Ching Arno Villringer Dalia Kasperaviciute Han G. Brunner Srdjan Djurovic Lachlan T. Strike Albert V. Smith Lars T. Westlye Paul A. Nyquist Bertram Müller-Myhsok Phil Lee Qiong Yang Herve Lemaitre Andreas Meyer-Lindenberg Vidar M. Steen Marc M. Bohlken Rachel M. Brouwer Charles DeCarli Mar Matarin Fabrice Crivello Henry Völzke Manuel Mattheisen Bruno Vellas Loes M. Olde Loohuis Sudha Seshadri Claudia L. Satizabal Sebastian Mohnke David C. Liewald Li Shen Kwangsik Nho Simon E. Fisher Deborah Janowitz Wiro J. Niessen Matthew J. Huentelman Sylvane Desrivières Ole A. Andreassen Evan Fletcher Christiane Wolf Vilmundur Gudnason Alejandro Arias-Vasquez Charles C. White Joshua C. Bis Pauline Maillard Ingrid Agartz Oliver Grimm Matthias Nauck Andrew M. McIntosh Iryna O. Fedko Gianpiero L. Cavalleri Andreas Heinz Tulio Guadalupe Andrew D. Johnson Daan van Rooij Thomas W. Mühleisen Jessica A. Turner Marieke Klein Jia Yu Koh Avram J. Holmes Saud Alhusaini Douglas N. Greve Roberto Roiz-Santiañez Nic J.A. van der Wee Irina Filippi Hans van Bokhoven Miguel E. Rentería Andrew J. Saykin Marjolein M.J. van Donkelaar Dan J. Stein Randy L. Gollub Sanjay M. Sisodiya Honghuang Lin Aaron Goldman Patrizia Mecocci Thomas Espeseth Barbara Franke Unn K. Haukvik Theo G.M. van Erp Venkata S. Mattay Jonathan C Ipser Catharina A. Hartman Florian Holsboer Saskia P. Hagenaars Benedicto Crespo-Facorro Manon Bernard Jerome I. Rotter Louis N. Vinke Nastassja Koen Vince D. Calhoun Anders M. Dale Dennis van der Meer Jordan W. Smoller Debra A. Fleischman Janita Bralten Hannah J. Jones Lavinia Athanasiu Hilleke E. Hulshoff Pol Brenda W.J.H. Penninx Peter R. Schofield Roel A. Ophoff J Wardlaw Sven J. van der Lee Katie L. McMahon Esther Walton Nicholas G. Martin Gunter Schumann Katharina Wittfeld Perminder S. Sachdev André G. Uitterlinden Christophe Tzourio Pieter J. Hoekstra Roberto Toro Henry Brodaty Marcella Rietschel David Ames George Davey Smith G. Bruce Pike Alexa S. Beiser Zdenka Pausova Simon Lovestone Robert C. Green Greig I. de Zubicaray Stephen M. Lawrie Mark E. Bastin Marco P. Boks M. Mallar Chakravarty Magda Tsolaki Myriam Fornage Nanda Rommelse Andre F. Marquand Anbupalam Thalamuthu Helena Schmidt Jason L. Stein Bruce M. Psaty Jan K. Buitelaar Jean-Luc Martinot Kazima B. Bulayeva Henrik Walter Xueqiu Jian Yasaman Saba Saima Hilal Paul M. Thompson Tamara B. Harris Jaap Oosterlaan Marie-José van Tol Joshua L. Roffman Bernard Mazoyer Shuo Li Nhat Trung Doan Qiang Chen John B.J. Kwok Najaf Amin Diana Tordesillas-Gutiérrez Eco J. C. de Geus Meike W. Vernooij Andrew J. Schork Susanne Erk Daniel R. Weinberger Grant W. Montgomery Jean Shin James T. Becker Martine Hoogman Philip L. De Jager Dirk J. Heslenfeld Derrek P. Hibar Narelle K. Hansell Andrew Simmons Micael Andersson Lucija Abramovic Dorret I. Boomsma Allison Stevens Wei Wen A. Veronica Witte Owen Carmichael Jayandra J. Himali Asta Håberg Hieab H.H. Adams Nynke A. Groenewold Sven Cichon Wiepke Cahn Lianne Schmaal Shannon L. Risacher Erik G. Jönsson Shahrzad Kharabian Masouleh Oliver Gruber Tianye Jia Hilkka Soininen M. Kamran Ikram Markus Loeffler Philipp G. Sämann Sungeun Kim Jingyun Yang Iwona Kłoszewska Ryota Kanai Christopher D. Whelan Massimo Pandolfo Dick J. Veltman Diane M. Becker Anouk den Braber Hans J. Grabe Neda Jahanshad Yanhui Hu Anita L. DeStefano Beng-Choon Ho Stephanie Le Hellard Cornelia M. van Duijn Georg Homuth Tomáš Paus Stéphanie Debette Nicola J. Armstrong Jouke-Jan Hottenga Eric Westman Tom V. Lee Sarah E. Medland Randy L. Buckner Benno Pütz Edith Hofer Steven G. Potkin Albert Hofman Dennis van 't Ent Sudheer Giddaluru Tatiana Foroud Guillén Fernández John D. Eicher Gareth E. Davies Thomas H. Mosley Michelle Luciano Lenore J. Launer Joshua W. Cheung Markus Scholz D. Höhn Thomas Wolfers Reinhold Schmidt Arthur W. Toga René S. Kahn Nazanin Karbalai Yuri Milaneschi Margaret J. Wright Martina Papmeyer David A. Bennett M. Arfan Ikram Stefan Ehrlich Marcel P. Zwiers Karen A. Mather Joshua M. Shulman
Publication Year :
2017
Publisher :
Cold Spring Harbor Laboratory, 2017.
Abstract
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.