Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
Publié le -
Nature Genetics
Auteurs :
Luis García-Marín, Adrian Campos, Santiago Diaz-Torres, Jill Rabinowitz, Zuriel Ceja, Brittany Mitchell, Katrina Grasby, Jackson Thorp, Ingrid Agartz, Saud Alhusaini, David Ames, Philippe Amouyel, Ole Andreassen, Konstantinos Arfanakis, Alejandro Arias-Vasquez, Nicola Armstrong, Lavinia Athanasiu, Mark Bastin, Alexa Beiser, David Bennett, Joshua Bis, Marco Boks, Dorret Boomsma, Henry Brodaty, Rachel Brouwer, Jan Buitelaar, Ralph Burkhardt, Wiepke Cahn, Vince Calhoun, Owen Carmichael, Mallar Chakravarty, Qiang Chen, Christopher Ching, Sven Cichon, Benedicto Crespo-Facorro, Fabrice Crivello, Anders Dale, George Davey Smith, Eco de Geus, Philip de Jager, Greig de Zubicaray, Stéphanie Debette, Charles Decarli, Chantal Depondt, Sylvane Desrivières, Srdjan Djurovic, Stefan Ehrlich, Susanne Erk, Thomas Espeseth, Guillén Fernández, Irina Filippi, Simon Fisher, Debra Fleischman, Evan Fletcher, Myriam Fornage, Andreas Forstner, Clyde Francks, Barbara Franke, Tian Ge, Aaron Goldman, Hans Grabe, Robert Green, Oliver Grimm, Nynke Groenewold, Oliver Gruber, Vilmundur Gudnason, Asta Håberg, Unn Haukvik, Andreas Heinz, Derrek Hibar, Saima Hilal, Jayandra Himali, Beng-Choon Ho, David Hoehn, Pieter Hoekstra, Edith Hofer, Wolfgang Hoffmann, Avram Holmes, Georg Homuth, Norbert Hosten, M. Kamran Ikram, Jonathan Ipser, Clifford Jack Jr, Neda Jahanshad, Erik Jönsson, Rene Kahn, Ryota Kanai, Marieke Klein, Maria Knol, Lenore Launer, Stephen Lawrie, Stephanie Le Hellard, Phil Lee, Hervé Lemaître, Shuo Li, David Liewald, Honghuang Lin, W T Longstreth, Oscar Lopez, Michelle Luciano, Pauline Maillard, Andre Marquand, Nicholas Martin, Jean-Luc Martinot, Karen Mather, Venkata Mattay, Katie Mcmahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Nazanin Mirza-Schreiber, Yuri Milaneschi, Thomas Mosley, Thomas Mühleisen, Bertram Müller-Myhsok, Susana Muñoz Maniega, Matthias Nauck, Kwangsik Nho, Wiro Niessen, Markus Nöthen, Paul Nyquist, Jaap Oosterlaan, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda Penninx, G. Bruce Pike, Bruce Psaty, Benno Pütz, Simone Reppermund, Marcella Rietschel, Shannon Risacher, Nina Romanczuk-Seiferth, Rafael Romero-Garcia, Gennady Roshchupkin, Jerome Rotter, Perminder Sachdev, Philipp Sämann, Arvin Saremi, Muralidharan Sargurupremraj, Andrew Saykin, Lianne Schmaal, Helena Schmidt, Reinhold Schmidt, Peter Schofield, Markus Scholz, Gunter Schumann, Emanuel Schwarz, Li Shen, Jean Shin, Sanjay Sisodiya, Albert Smith, Jordan Smoller, Hilkka Soininen, Vidar Steen, Dan Stein, Jason Stein, Sophia Thomopoulos, Arthur Toga, Diana Tordesillas-Gutiérrez, Julian Trollor, Maria Valdes-Hernandez, Dennis van ′t Ent, Hans van Bokhoven, Dennis van der Meer, Nic van der Wee, Javier Vázquez-Bourgon, Dick Veltman, Meike Vernooij, Arno Villringer, Louis Vinke, Henry Völzke, Henrik Walter, Joanna Wardlaw, Daniel Weinberger, Michael Weiner, Wei Wen, Lars Westlye, Eric Westman, Tonya White, A. Veronica Witte, Christiane Wolf, Jingyun Yang, Marcel Zwiers, M. Arfan Ikram, Sudha Seshadri, Paul Thompson, Claudia Satizabal, Sarah Medland, Miguel Rentería
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson's disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases.
