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

description: 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.