Hibar, Derrek P. and Stein, Jason L. and Renteria, Miguel E. and Arias-Vasquez, Alejandro and Desrivières, Sylvane and Jahanshad, Neda and Toro, Roberto and Wittfeld, Katharina and Abramovic, Lucija and Andersson, Micael and Aribisala, Benjamin S. and Armstrong, Nicola J. and Bernard, Manon and Bohlken, Marc M. and Boks, Marco P. and Bralten, Janita and Brown, Andrew A. and Mallar Chakravarty, M. and Chen, Qiang and Ching, Christopher R. 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H. and Green, Robert C. and Guelfi, Sebastian and Hansell, Narelle K. and Hartman, Catharina A. and Hegenscheid, Katrin and Heinz, Andreas and Hernandez, Dena G. and Heslenfeld, Dirk J. and Hoekstra, Pieter J. and Holsboer, Florian and Homuth, Georg and Hottenga, Jouke-Jan and Ikeda, Masashi and Jack, Clifford R. and Jenkinson, Mark and Johnson, Robert and Kanai, Ryota and Keil, Maria and Kent, Jack W. and Kochunov, Peter and Kwok, John B. and Lawrie, Stephen M. and Liu, Xinmin and Longo, Dan L. and McMahon, Katie L. and Meisenzahl, Eva and Melle, Ingrid and Mohnke, Sebastian and Montgomery, Grant W. and Mostert, Jeanette C. and Mühleisen, Thomas W. and Nalls, Michael A. and Nichols, Thomas E. and Nilsson, Lars G. and Nöthen, Markus M. and Ohi, Kazutaka and Olvera, Rene L. and Perez-Iglesias, Rocio and Bruce Pike, G. and Potkin, Steven G. and Reinvang, Ivar and Reppermund, Simone and Rietschel, Marcella and Romanczuk-Seiferth, Nina and Rosen, Glenn D. and Rujescu, Dan and Schnell, Knut and Schofield, Peter R. and Smith, Colin and Steen, Vidar M. and Sussmann, Jessika E. and Thalamuthu, Anbupalam and Toga, Arthur W. and Traynor, Bryan J. and Troncoso, Juan and Turner, Jessica A. and Valdés Hernández, Maria C. and van 't Ent, Dennis and van der Brug, Marcel and van der Wee, Nic J. 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Abstract

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.

Item Type:	Article
Keywords:	Common genetic variants; influence; human; subcortical; brain structures;
Academic Unit:	Faculty of Science and Engineering > Biology Faculty of Science and Engineering > Research Institutes > Human Health Institute
Item ID:	17224
Identification Number:	https://doi.org/10.1038/nature14101
Depositing User:	Lorna Lopez
Date Deposited:	24 May 2023 10:59
Journal or Publication Title:	Nature Communications
Publisher:	Nature Publshing Group
Refereed:	Yes
URI:	Publisher
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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