Genetic variants associated with longitudinal changes in brain structure across the lifespan
Publié le -
Nature Neuroscience
Auteurs :
Rachel Brouwer, Marieke Klein, Katrina Grasby, Hugo Schnack, Neda Jahanshad, Jalmar Teeuw, Sophia Thomopoulos, Emma Sprooten, Carol Franz, Nitin Gogtay, William Kremen, Matthew Panizzon, Loes Olde Loohuis, Christopher Whelan, Moji Aghajani, Clara Alloza, Dag Alnæs, Eric Artiges, Rosa Ayesa-Arriola, Gareth Barker, Mark Bastin, Elisabet Blok, Erlend Bøen, Isabella Breukelaar, Joanna Bright, Elizabeth Buimer, Robin Bülow, Dara Cannon, Simone Ciufolini, Nicolas Crossley, Christienne Damatac, Paola Dazzan, Casper de Mol, Sonja de Zwarte, Sylvane Desrivières, Covadonga Díaz-Caneja, Nhat Trung Doan, Katharina Dohm, Juliane Fröhner, Janik Goltermann, Antoine Grigis, Dominik Grotegerd, Laura Han, Mathew Harris, Catharina Hartman, Sarah Heany, Walter Heindel, Dirk Heslenfeld, Sarah Hohmann, Bernd Ittermann, Philip Jansen, Joost Janssen, Tianye Jia, Jiyang Jiang, Christiane Jockwitz, Temmuz Karali, Daniel Keeser, Martijn Koevoets, Rhoshel Lenroot, Berend Malchow, René Mandl, Vicente Medel, Susanne Meinert, Catherine Morgan, Thomas Mühleisen, Leila Nabulsi, Nils Opel, Víctor Ortiz-García de la Foz, Bronwyn Overs, Marie-Laure Paillère Martinot, Ronny Redlich, Tiago Reis Marques, Jonathan Repple, Gloria Roberts, Gennady Roshchupkin, Nikita Setiaman, Elena Shumskaya, Frederike Stein, Gustavo Sudre, Shun Takahashi, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Aad van der Lugt, Neeltje van Haren, Joanna Wardlaw, Wei Wen, Henk-Jan Westeneng, Katharina Wittfeld, Alyssa Zhu, Andre Zugman, Nicola Armstrong, Gaia Bonfiglio, Janita Bralten, Shareefa Dalvie, Gail Davies, Marta Di Forti, Linda Ding, Gary Donohoe, Andreas Forstner, Javier Gonzalez-Peñas, Joao Guimaraes, Georg Homuth, Jouke-Jan Hottenga, Maria Knol, John Kwok, Stephanie Le Hellard, Karen Mather, Yuri Milaneschi, Derek Morris, Markus Nöthen, Sergi Papiol, Marcella Rietschel, Marcos Santoro, Vidar Steen, Jason Stein, Fabian Streit, Rick Tankard, Alexander Teumer, Dennis van 'T Ent, Dennis van der Meer, Kristel van Eijk, Evangelos Vassos, Javier Vázquez-Bourgon, Stephanie Witt, Hieab Adams, Ingrid Agartz, David Ames, Katrin Amunts, Ole Andreassen, Celso Arango, Tobias Banaschewski, Bernhard Baune, Sintia Belangero, Arun Bokde, Dorret Boomsma, Rodrigo Bressan, Henry Brodaty, Jan Buitelaar, Wiepke Cahn, Svenja Caspers, Sven Cichon, Benedicto Crespo-Facorro, Simon Cox, Udo Dannlowski, Torbjørn Elvsåshagen, Thomas Espeseth, Peter Falkai, Simon Fisher, Herta Flor, Janice Fullerton, Hugh Garavan, Penny Gowland, Hans Grabe, Tim Hahn, Andreas Heinz, Manon Hillegers, Jacqueline Hoare, Pieter Hoekstra, Mohammad Ikram, Andrea Jackowski, Andreas Jansen, Erik Jönsson, Rene Kahn, Tilo Kircher, Mayuresh Korgaonkar, Axel Krug, Hervé Lemaître, Ulrik Malt, Jean-Luc Martinot, Colm McDonald, Philip Mitchell, Ryan Muetzel, Robin Murray, Frauke Nees, Igor Nenadić, Jaap Oosterlaan, Roel Ophoff, Pedro Pan, Brenda Penninx, Luise Poustka, Perminder Sachdev, Giovanni Salum, Peter Schofield, Gunter Schumann, Philip Shaw, Kang Sim, Michael Smolka, Dan Stein, Julian Trollor, Leonard van den Berg, Jan Veldink, Henrik Walter, Lars Westlye, Robert Whelan, Tonya White, Margaret Wright, Sarah Medland, Barbara Franke, Paul Thompson, Hilleke Hulshoff Pol, Rüdiger Brühl, Dimitri Papadopoulos Orfanos, Tomáš Paus, Sabina Millenet
Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging.
