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Common genetic variants influence human subcortical brain structures

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posted on 2023-06-09, 19:27 authored by Derrek P Hibar, Jason L Stein, Miguel E Renteria, Alejandro Arias-Vasquez, Sylvane Desrivières, Neda Jahanshad, Roberto Toro, Katharina Wittfeld, Lucija Abramovic, Micael Andersson, Benjamin S Aribisala, Nicola J Armstrong, Manon Bernard, Marc M Bohlken, Marco P Boks, Janita Bralten, Andrew A Brown, M. Mallar Chakravarty, Qiang Chen, Christopher R K Ching, Gabriel Cuellar-Partida, Anouk den Braber, Sudheer Giddaluru, Aaron L Goldman, Oliver Grimm, Tulio Guadalupe, Johanna Hass, Girma Woldehawariat, Avram J Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, Loes M. Olde Loohuis, Michelle Luciano, Christine Macare, Karen A. Mather, Manuel Mattheisen, Yuri Milaneschi, Kwangsik Nho, Martina Papmeyer, Adaikalavan Ramasamy, Shannon L Risacher, Roberto Roiz-Santiañez, Emma J Rose, Alireza Salami, Philipp G Sämann, Lianne Schmaal, Andrew J Schork, Jean Shin, Lachlan T Strike, Alexander Teumer, Marjolein M J van Donkelaar, Kristel R van Eijk, Raymond K Walters, Lars T Westlye, Christopher D Whelan, Anderson M Winkler, Marcel P Zwiers, Saud Alhusaini, Lavinia Athanasiu, Stefan Ehrlich, Marina M H Hakobjan, Cecilie B Hartberg, Unn K Haukvik, Angelien J G A M Heister, David Hoehn, Dalia Kasperaviciute, David C M Liewald, Lorna M Lopez, Remco R R Makkinje, Mar Matarin, Marlies A M Naber, D Reese McKay, Margaret Needham, Allison C Nugent, Benno Pütz, Natalie A Royle, Li Shen, Emma Sprooten, Daniah Trabzuni, Saskia S L van der Marel, Kimm J E van Hulzen, Esther Walton, Christiane Wolf, Ryota Kanai, The Alzheimer's Disease Neuroimaging Initiative, The CHARGE Consortium, EPIGEN, IMAGEN, SYS, Nicholas G Martin, Margaret J Wright, Gunter Schumann, Barbara Franke, Paul M Thompson, Sarah E Medland, others
The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. 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 volume5 and intracranial volume6. 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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