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Common genetic variants influence human subcortical brain structures

Authors
Derrek Hibar,Jason Stein
Miguel Rentería,Alejandro Vásquez,Sylvane Desrivières,Neda Jahanshad,Roberto Toro,Katharina Wittfeld,Lucija Abramovic,Micael Andersson,Benjamin Aribisala,Nicola Armstrong,Manon Bernard,Marc Bohlken,Marco Boks,Janita Bralten,Andrew Brown,M. Chakravarty,Qiang Chen,Christopher Ching,Gabriel Cuéllar-Partida,Anouk Braber,Sudheer Giddaluru,Aaron Goldman,O. Grimm,Tulio Guadalupe,Johanna Haß,Girma Woldehawariat,Avram Holmes,Martine Hoogman,Deborah Janowitz,Tianye Jia,Sungeun Kim,Marieke Klein,Bernd Krämer,Phil Lee,Loes Loohuis,Michelle Luciano,Christine Macare,Karen Mather,Manuel Mattheisen,Yuri Milaneschi,Kwangsik Nho,Martina Papmeyer,Adaikalavan Ramasamy,Shannon Risacher,Roberto Roiz‐Santiáñez,Emma Rose,Alireza Salami,Philipp Sämann,Lianne Schmaal,Andrew Schork,Jean Shin,Lachlan Strike,Alexander Teumer,Marjolein Donkelaar,Kelly Williams,Raymond Walters,Lars Westlye,Christopher Whelan,Anderson Winkler,Marcel Zwiers,Saud Alhusaini,Lavinia Athanasiu,Stefan Ehrlich,Marina Hakobjan,Cecilie Hartberg,Unn Haukvik,Angelien Heister,David Hoehn,Dalia Kasperavičiūtė,David Liewald,Lorna Lopez,Remco Makkinje,Sebastian Guelfi,Marlies Naber,Dean McKay,Margaret Needham,Allison Nugent,Benno Pütz,Natalie Royle,Li Shen,Emma Sprooten,Daniah Trabzuni,Saskia Marel,K.J.E. Hulzen,Esther Walton,Christiane Wolf,Laura Almasy,David Ames,Henk Berendse,Amelia Assareh,Mark Bastin,Henry Brodaty,Kazima Bulayeva,Melanie Carless,Sven Cichon,Aiden Corvin,Joanne Curran,Michael Czisch,Greig Zubicaray,Allissa Dillman,Ravi Duggirala,Thomas Dyer,Susanne Erk,Iryna Fedko,Luigi Ferrucci,Tatiana Foroud,Peter Fox,Masaki Fukunaga,J. Gibbs,Harald Göring,Robert Green,Narelle Hansell,Catharina Hartman,Katrin Hegenscheid,Andreas Heinz,Dena Hernández,Dirk Heslenfeld,Pieter Hoekstra,Herta Flor,Georg Homuth,Jouke‐Jan Hottenga,Masashi Ikeda,Clifford Jack,Mark Jenkinson,R. Johnson,Ryota Kanai,Maria Keil,Jack Kent,Peter Kochunov,John Kwok,Stephen Lawrie,Xinmin Liu,Dan Longo,Katie McMahon,Eva Meisenzahl,Ingrid Melle,Sebastian Mohnke,Grant Montgomery,Jeanette Mostert,Thomas Mühleisen,Michael Weale,Thomas Nichols,Lars Nilsson,Markus Nöthen,Kazutaka Ohi,Rene Olvera,Rocío Pérez‐Iglesias,G. Pike,Steven Potkin,Ivar Reinvang,Simone Reppermund,Marcella Rietschel,Nina Romanczuk‐Seiferth,Glenn Rosen,Dan Rujescu,Knut Schnell,Peter Schofield,Colin Smith,Vidar Steen,Jessika Sussmann,Anbupalam Thalamuthu,Arthur Toga,Bryan Traynor,Juan Troncoso,Jessica Turner,Maria Hernández,Dennis Ent,Marcel Brug,Nic Wee,Marie‐José Tol,Dick Veltman,Thomas Wassink,Eric Westman,Ronald Zielke,Alan Zonderman,David Ashbrook,Reinmar Hager,Lu Lu,Francis McMahon,Derek Morris,Robert Williams,Han Brunner,Randy Buckner,Jan Buitelaar,Wiepke Cahn,Vince Calhoun,Gianpiero Cavalleri,Benedicto Crespo‐Facorro,Anders Dale,Gareth Davies,Norman Delanty,Chantal Depondt,Srdjan Djurovic,Wayne Drevets,Thomas Espeseth,Randy Gollub,Beng‐Choon Ho,Richa Gupta,Norbert Hosten,René Kahn,Stéphanie Hellard,Andreas Meyer‐Lindenberg,Bertram Müller‐Myhsok,Matthias Nauck,Lars Nyberg,Massimo Pandolfo,Brenda Penninx,Joshua Roffman,Sanjay Sisodiya,Jordan Smoller,Hans Bokhoven,Neeltje Haren,Henry Völzke,Henrik Walter,Michael Weiner,Wei Wen,Tonya White,Ingrid Agartz,Ole Andreassen,John Blangero,Dorret Boomsma,Rachel Brouwer,Dara Cannon,Mark Cookson,Eco Geus,Ian Deary,Gary Donohoe,Guillén Fernández,Simon Fisher,Clyde Francks,David Glahn,Hans Grabe,Oliver Gruber,John Hardy,Ryota Hashimoto,Hilleke Pol,Erik Jönsson,Iwona Kłoszewska,Simon Lovestone,Venkata Mattay,Patrizia Mecocci,Colm McDonald,Andrew McIntosh,Roel Ophoff,Tomáš Paus,Zdenka Pausová,Mina Ryten,Perminder Sachdev,Andrew Saykin,Andy Simmons,Hilkka Soininen,Joanna Wardlaw,Daniel Weinberger,Hieab Adams,Lenore Launer,Stephan Seiler,Reinhold Schmidt,Ganesh Chauhan,Sudha Seshadri,James Walters,Lisa Yanek,Sven Lee,Maritza Ebling,Bruce Fischl,W.T. Longstreth,Douglas Greve,Helena Schmidt,Paul Nyquist,Louis Vinke,Cornelia Duijn,Luting Xue,Bernard Mazoyer,Joshua Bis,Vilmundur Guðnason,M. Ikram,Nicholas Martin,Margaret Wright,Günter Schumann,Barbara Franke,Paul Thompson
+280 authors
,Sarah Medland
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Jan 20, 2015
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Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. 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 volume and intracranial volume. 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.

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