Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
García-Marín, Luis M.; Campos, Adrian I.; Diaz-Torres, Santiago; Rabinowitz, Jill A.; Ceja, Zuriel; Mitchell, Brittany L.; Grasby, Katrina L.; Thorp, Jackson G.; Agartz, Ingrid; Alhusaini, Saud; Ames, David; Amouyel, Philippe; Andreassen, Ole A.; Arfanakis, Konstantinos; Arias-Vasquez, Alejandro; Armstrong, Nicola J.; Athanasiu, Lavinia; Bastin, Mark E.; Beiser, Alexa S.; Bennett, David A.; Bis, Joshua C.; Boks, Marco P.M.; Boomsma, Dorret I.; Brodaty, Henry; Brouwer, Rachel M.; Buitelaar, Jan K.; Burkhardt, Ralph; Cahn, Wiepke; Calhoun, Vince D.; Carmichael, Owen T.; Chakravarty, Mallar; Chen, Qiang; Ching, Christopher R.K.; Cichon, Sven; Crespo-Facorro, Benedicto; Crivello, Fabrice; Dale, Anders M.; Smith, George Davey; de Geus, Eco J.C.; De Jager, Philip L.; de Zubicaray, Greig I.; Debette, Stéphanie; DeCarli, Charles; Depondt, Chantal; Desrivières, Sylvane; Djurovic, Srdjan; Ehrlich, Stefan; Erk, Susanne; Espeseth, Thomas; Fernández, Guillén; Filippi, Irina; Fisher, Simon E.; Fleischman, Debra A.; Fletcher, Evan; Fornage, Myriam; Forstner, Andreas J.; Francks, Clyde; Franke, Barbara; Ge, Tian; Goldman, Aaron L.; Grabe, Hans J.; Green, Robert C.; Grimm, Oliver; Groenewold, Nynke A.; Gruber, Oliver; Gudnason, Vilmundur; Håberg, Asta K.; Haukvik, Unn K.; Heinz, Andreas; Hibar, Derrek P.; Hilal, Saima; Himali, Jayandra J.; Ho, Beng Choon; Hoehn, David F.; Hoekstra, Pieter J.; Hofer, Edith; Hoffmann, Wolfgang; Holmes, Avram J.; Homuth, Georg; Hosten, Norbert; Ikram, M. Kamran; Ipser, Jonathan C.; Jack, Clifford R.; Jahanshad, Neda; Jönsson, Erik G.; Kahn, Rene S.; Kanai, Ryota; Klein, Marieke; Knol, Maria J.; Launer, Lenore J.; Lawrie, Stephen M.; Hellard, Stephanie Le; Lee, Phil H.; Lemaître, Hervé; Li, Shuo; Liewald, David C.M.; Lin, Honghuang; Longstreth, W. T.; Lopez, Oscar L.; Luciano, Michelle; Maillard, Pauline; Marquand, Andre F.; Martin, Nicholas G.; Martinot, Jean Luc; Mather, Karen A.; Mattay, Venkata S.; McMahon, Katie L.; Mecocci, Patrizia; Melle, Ingrid; Meyer-Lindenberg, Andreas; Mirza-Schreiber, Nazanin; Milaneschi, Yuri; Mosley, Thomas H.; Mühleisen, Thomas W.; Müller-Myhsok, Bertram; Maniega, Susana Muñoz; Nauck, Matthias; Nho, Kwangsik; Niessen, Wiro J.; Nöthen, Markus M.; Nyquist, Paul A.; Oosterlaan, Jaap; Pandolfo, Massimo; Paus, Tomas; Pausova, Zdenka; Penninx, Brenda W.J.H.; Pike, G. Bruce; Psaty, Bruce M.; Pütz, Benno; Reppermund, Simone; Rietschel, Marcella D.; Risacher, Shannon L.; Romanczuk-Seiferth, Nina; Romero-Garcia, Rafael; Roshchupkin, Gennady V.; Rotter, Jerome I.; Sachdev, Perminder S.; Sämann, Philipp G.; Saremi, Arvin; Sargurupremraj, Muralidharan; Saykin, Andrew J.; Schmaal, Lianne; Schmidt, Helena; Schmidt, Reinhold; Schofield, Peter R.; Scholz, Markus; Schumann, Gunter; Schwarz, Emanuel; Shen, Li; Shin, Jean; Sisodiya, Sanjay M.; Smith, Albert V.; Smoller, Jordan W.; Soininen, Hilkka S.; Steen, Vidar M.; Stein, Dan J.; Stein, Jason L.; Thomopoulos, Sophia I.; Toga, Arthur W.; Tordesillas-Gutiérrez, Diana; Trollor, Julian N.; Valdes-Hernandez, Maria C.; van ′t Ent, Dennis; van Bokhoven, Hans; van der Meer, Dennis; van der Wee, Nic J.A.; Vázquez-Bourgon, Javier; Veltman, Dick J.; Vernooij, Meike W.; Villringer, Arno; Vinke, Louis N.; Völzke, Henry; Walter, Henrik; Wardlaw, Joanna M.; Weinberger, Daniel R.; Weiner, Michael W.; Wen, Wei; Westlye, Lars T.; Westman, Eric; White, Tonya; Witte, A. Veronica; Wolf, Christiane; Yang, Jingyun; Zwiers, Marcel P.; Ikram, M. Arfan; Seshadri, Sudha; Thompson, Paul M.; Satizabal, Claudia L.; Medland, Sarah E.; Rentería, Miguel E.
(2024) Nature genetics, volume 56, issue 11, pp. 2333 - 2344
(Article)
Abstract
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
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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.
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Keywords: Genetics
ISSN: 1061-4036
Publisher: Nature Research
Note: Publisher Copyright: © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
(Peer reviewed)