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Common genetic variants influence human subcortical brain structures

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 Chakravarty, M. Mallar and Chen, Qiang and Ching, Christopher R. 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A. and van Tol, Marie-Jose and Dick J., Veltman and Wassink, Thomas H. and Westman, Eric and Zielke, Ronald H. and Zonderman, Alan B. and Ashbrook, David G. and Hager, Reinmar and Lu, Lu and McMahon, Francis J. and Morris, Derek W. and Williams, Robert W. and Brunner, Han G. and Buckner, Randy L. and Buitelaar, Jan K. and Cahn, Wiepke and Calhoun, Vince D. and Cavalleri, Gianpiero L. and Crespo-Facorro, Benedicto and Dale, Anders M. and Davies, Gareth E. and Delanty, Norman and Depondt, Chantal and Djurovic, Srdjan and Drevets, Wayne C. and Espeseth, Thomas and Gollub, Randy L. and Ho, Beng-Choon and Hoffmann, Wolfgang and Hosten, Norbert and Kahn, René S. and Le Hellard, Stephanie and Meyer-Lindenberg, Andreas and Müller-Myhsok, Bertram and Nauck, Matthias and Nyberg, Lars and Pandolfo, Massimo and Penninx, Brenda W. J. H. and Roffman, Joshua L. and Sisodiya, Sanjay M. and Smoller, Jordan W. and van Bokhoven, Hans and van Haren, Neeltje E. 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H. and Launer, Lenore J. and Seiler, Stephan and Schmidt, Reinhold and Chauhan, Ganesh and Satizabal, Claudia L. and Becker, James T. and Yanek, Lisa and van der Lee, Sven J. and Ebling, Maritza and Fischl, Bruce and Longstreth Jr, W. T. and Greve, Douglas and Schmidt, Helena and Nyquist, Paul and Vinke, Louis N. and van Duijn, Cornelia M. and Xue, Luting and Mazoyer, Bernard and Bis, Joshua C. and Gudnason, Vilmundur and Seshadri, Sudha and Ikram, M. Arfan and The Alzheimer’s Disease Neuroimaging Initiative, and The CHARGE Consortium, and EPIGEN, and IMAGEN, and SYS, and Martin, Nicholas G. and Wright, Margaret J. and Schumann, Gunter and Franke, Barbara and Thompson, Paul M. and Medland, Sarah E.. (2015) Common genetic variants influence human subcortical brain structures. Nature, 520 (7546). pp. 224-229.

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Official URL: https://edoc.unibas.ch/61552/

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Abstract

The highly complex structure of the human brain is strongly shaped by genetic influences. Subcortical brain regions form circuits with cortical areas to coordinate movement, learning, memory and motivation, and altered circuits can lead to abnormal behaviour and disease. 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 volume and intracranial volume. 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 x 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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
ISSN:0028-0836
e-ISSN:1476-4687
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:22 Sep 2018 13:59
Deposited On:22 Sep 2018 13:59

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