Common genetic variants influence human subcortical brain structures
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 ge...
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| Hauptverfasser: | , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
9 April 2015
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| In: |
Nature
Year: 2015, Jahrgang: 520, Heft: 7546, Pages: 224-229 |
| ISSN: | 1476-4687 |
| DOI: | 10.1038/nature14101 |
| Online-Zugang: | Verlag, Volltext: http://dx.doi.org/10.1038/nature14101 Verlag, Volltext: http://www.nature.com.ezproxy.medma.uni-heidelberg.de/nature/journal/v520/n7546/full/nature14101.html 
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| Verfasserangaben: | 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, Laura Almasy, David Ames, Sampath Arepalli, Amelia A. Assareh, Mark E. Bastin, Henry Brodaty, Kazima B. Bulayeva, Melanie A. Carless, Sven Cichon, Aiden Corvin, Joanne E. Curran, Michael Czisch, Greig I. de Zubicaray, Allissa Dillman, Ravi Duggirala, Thomas D. Dyer, Susanne Erk, Iryna O. Fedko, Luigi Ferrucci, Tatiana M. Foroud, Peter T. Fox, Masaki Fukunaga, J. Raphael Gibbs, Harald H.H. Göring, Robert C. Green, Sebastian Guelfi, Narelle K. Hansell, Catharina A. Hartman, Katrin Hegenscheid, Andreas Heinz, Dena G. Hernandez, Dirk J. Heslenfeld, Pieter J. Hoekstra, Florian Holsboer, Georg Homuth, Jouke-Jan Hottenga, Masashi Ikeda, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Ryota Kanai, Maria Keil, Jack W. Kent Jr, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Xinmin Liu, Dan L. Longo, Katie L. McMahon, Eva Meisenzahl, Ingrid Melle, Sebastian Mohnke, Grant W. Montgomery, Jeanette C. Mostert, Thomas W. Mühleisen, Michael A. Nalls, Thomas E. Nichols, Lars G. Nilsson, Markus M. Nöthen, Kazutaka Ohi, Rene L. Olvera, Rocio Perez-Iglesias, G. Bruce Pike, Steven G. Potkin, Ivar Reinvang, Simone Reppermund, Marcella Rietschel, Nina Romanczuk-Seiferth, Glenn D. Rosen, Dan Rujescu, Knut Schnell, Peter R. Schofield, Colin Smith, Vidar M. Steen, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Jessica A. Turner, Maria C. Valdés Hernández, Dennis van 't Ent, Marcel van der Brug, Nic J.A. van der Wee, Marie-Jose van Tol, Dick J. Veltman, Thomas H. Wassink, Eric Westman, Ronald H. Zielke, Alan B. Zonderman, David G. Ashbrook, Reinmar Hager, Lu Lu, Francis J. McMahon, Derek W. Morris, Robert W. Williams, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Wiepke Cahn, Vince D. Calhoun, Gianpiero L. Cavalleri, Benedicto Crespo-Facorro, Anders M. Dale, Gareth E. Davies, Norman Delanty, Chantal Depondt, Srdjan Djurovic, Wayne C. Drevets, Thomas Espeseth, Randy L. Gollub, Beng-Choon Ho, Wolfgang Hoffmann, Norbert Hosten, René S. Kahn, Stephanie Le Hellard, Andreas Meyer-Lindenberg, Bertram Müller-Myhsok, Matthias Nauck, Lars Nyberg, Massimo Pandolfo, Brenda W.J.H. Penninx, Joshua L. Roffman, Sanjay M. Sisodiya, Jordan W. Smoller, Hans van Bokhoven, Neeltje E.M. van Haren, Henry Völzke, Henrik Walter, Michael W. Weiner, Wei Wen, Tonya White, Ingrid Agartz, Ole A. Andreassen, John Blangero, Dorret I. Boomsma, Rachel M. Brouwer, Dara M. Cannon, Mark R. Cookson, Eco J.C. de Geus, Ian J. Deary, Gary Donohoe, Guillén Fernández, Simon E. Fisher, Clyde Francks, David C. Glahn, Hans J. Grabe, Oliver Gruber, John Hardy, Ryota Hashimoto, Hilleke E. Hulshoff Pol, Erik G. Jönsson, Iwona Kloszewska, Simon Lovestone, Venkata S. Mattay, Patrizia Mecocci, Colm McDonald, Andrew M. McIntosh, Roel A. Ophoff, Tomas Paus, Zdenka Pausova, Mina Ryten, Perminder S. Sachdev, Andrew J. Saykin, Andy Simmons, Andrew Singleton, Hilkka Soininen, Joanna M. Wardlaw, Michael E. Weale, Daniel R. Weinberger, Hieab H.H. Adams, Lenore J. Launer, Stephan Seiler, Reinhold Schmidt, Ganesh Chauhan, Claudia L. Satizabal, James T. Becker, Lisa Yanek, Sven J. van der Lee, Maritza Ebling, Bruce Fischl, W. T. Longstreth Jr, Douglas Greve, Helena Schmidt, Paul Nyquist, Louis N. Vinke, Cornelia M. van Duijn, Luting Xue, Bernard Mazoyer, Joshua C. Bis, Vilmundur Gudnason, Sudha Seshadri, M. Arfan Ikram, 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 |
MARC
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| 245 | 1 | 0 | |a Common genetic variants influence human subcortical brain structures |c 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, Laura Almasy, David Ames, Sampath Arepalli, Amelia A. Assareh, Mark E. Bastin, Henry Brodaty, Kazima B. Bulayeva, Melanie A. Carless, Sven Cichon, Aiden Corvin, Joanne E. Curran, Michael Czisch, Greig I. de Zubicaray, Allissa Dillman, Ravi Duggirala, Thomas D. Dyer, Susanne Erk, Iryna O. Fedko, Luigi Ferrucci, Tatiana M. Foroud, Peter T. Fox, Masaki Fukunaga, J. Raphael Gibbs, Harald H.H. Göring, Robert C. Green, Sebastian Guelfi, Narelle K. Hansell, Catharina A. Hartman, Katrin Hegenscheid, Andreas Heinz, Dena G. Hernandez, Dirk J. Heslenfeld, Pieter J. Hoekstra, Florian Holsboer, Georg Homuth, Jouke-Jan Hottenga, Masashi Ikeda, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Ryota Kanai, Maria Keil, Jack W. Kent Jr, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Xinmin Liu, Dan L. Longo, Katie L. McMahon, Eva Meisenzahl, Ingrid Melle, Sebastian Mohnke, Grant W. Montgomery, Jeanette C. Mostert, Thomas W. Mühleisen, Michael A. Nalls, Thomas E. Nichols, Lars G. Nilsson, Markus M. Nöthen, Kazutaka Ohi, Rene L. Olvera, Rocio Perez-Iglesias, G. Bruce Pike, Steven G. Potkin, Ivar Reinvang, Simone Reppermund, Marcella Rietschel, Nina Romanczuk-Seiferth, Glenn D. Rosen, Dan Rujescu, Knut Schnell, Peter R. Schofield, Colin Smith, Vidar M. Steen, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Jessica A. Turner, Maria C. Valdés Hernández, Dennis van 't Ent, Marcel van der Brug, Nic J.A. van der Wee, Marie-Jose van Tol, Dick J. Veltman, Thomas H. Wassink, Eric Westman, Ronald H. Zielke, Alan B. Zonderman, David G. Ashbrook, Reinmar Hager, Lu Lu, Francis J. McMahon, Derek W. Morris, Robert W. Williams, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Wiepke Cahn, Vince D. Calhoun, Gianpiero L. Cavalleri, Benedicto Crespo-Facorro, Anders M. Dale, Gareth E. Davies, Norman Delanty, Chantal Depondt, Srdjan Djurovic, Wayne C. Drevets, Thomas Espeseth, Randy L. Gollub, Beng-Choon Ho, Wolfgang Hoffmann, Norbert Hosten, René S. Kahn, Stephanie Le Hellard, Andreas Meyer-Lindenberg, Bertram Müller-Myhsok, Matthias Nauck, Lars Nyberg, Massimo Pandolfo, Brenda W.J.H. Penninx, Joshua L. Roffman, Sanjay M. Sisodiya, Jordan W. Smoller, Hans van Bokhoven, Neeltje E.M. van Haren, Henry Völzke, Henrik Walter, Michael W. Weiner, Wei Wen, Tonya White, Ingrid Agartz, Ole A. Andreassen, John Blangero, Dorret I. Boomsma, Rachel M. Brouwer, Dara M. Cannon, Mark R. Cookson, Eco J.C. de Geus, Ian J. Deary, Gary Donohoe, Guillén Fernández, Simon E. Fisher, Clyde Francks, David C. Glahn, Hans J. Grabe, Oliver Gruber, John Hardy, Ryota Hashimoto, Hilleke E. Hulshoff Pol, Erik G. Jönsson, Iwona Kloszewska, Simon Lovestone, Venkata S. Mattay, Patrizia Mecocci, Colm McDonald, Andrew M. McIntosh, Roel A. Ophoff, Tomas Paus, Zdenka Pausova, Mina Ryten, Perminder S. Sachdev, Andrew J. Saykin, Andy Simmons, Andrew Singleton, Hilkka Soininen, Joanna M. Wardlaw, Michael E. Weale, Daniel R. Weinberger, Hieab H.H. Adams, Lenore J. Launer, Stephan Seiler, Reinhold Schmidt, Ganesh Chauhan, Claudia L. Satizabal, James T. Becker, Lisa Yanek, Sven J. van der Lee, Maritza Ebling, Bruce Fischl, W. T. Longstreth Jr, Douglas Greve, Helena Schmidt, Paul Nyquist, Louis N. Vinke, Cornelia M. van Duijn, Luting Xue, Bernard Mazoyer, Joshua C. Bis, Vilmundur Gudnason, Sudha Seshadri, M. Arfan Ikram, 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 |
| 264 | 1 | |c 9 April 2015 | |
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| 520 | |a 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 × 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. | ||
| 650 | 4 | |a Behavioural genetics | |
| 650 | 4 | |a Biochemistry | |
| 650 | 4 | |a Biophysics | |
| 650 | 4 | |a Biosensors | |
| 650 | 4 | |a Genetics of the nervous system | |
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