Novel genetic loci underlying human intracranial volume identified through genome-wide association
Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unk...
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| Main Authors: | , , , , |
|---|---|
| Format: | Article (Journal) |
| Language: | English |
| Published: |
3 October 2016
|
| In: |
Nature neuroscience
Year: 2016, Volume: 19, Issue: 12, Pages: 1569-1582 |
| ISSN: | 1546-1726 |
| DOI: | 10.1038/nn.4398 |
| Online Access: | Verlag, Volltext: http://dx.doi.org/10.1038/nn.4398 Verlag, Volltext: http://www.nature.com/articles/nn.4398 
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| Author Notes: | Hieab H. H. Adams, Derrek P. Hibar, Vincent Chouraki, Jason L. Stein, Paul A. Nyquist, Miguel E. Rentería, Stella Trompet, Alejandro Arias-Vasquez, Sudha Seshadri, Sylvane Desrivières, Ashley H. Beecham, Neda Jahanshad, Katharina Wittfeld, Sven J. Van der Lee, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Alexa Beiser, Manon Bernard, Joshua C. Bis, Laura M. E. Blanken, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Ganesh Chauhan, Qiang Chen, Christopher R. K. Ching, Gabriel Cuellar-Partida, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Irina Filippi, Tian Ge, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, Corina U. Greven, Oliver Grimm, Michael E. Griswold, Tulio Guadalupe, Johanna Hass, Unn K. Haukvik, Saima Hilal, Edith Hofer, David Hoehn, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Dalia Kasperaviciute, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, Jiemin Liao, David C. M. Liewald, Lorna M. Lopez, Michelle Luciano, Christine Macare, Andre Marquand, Mar Matarin, Karen A. Mather, Manuel Mattheisen, Bernard Mazoyer, David R. McKay, Rebekah McWhirter, Yuri Milaneschi, Nazanin Mirza-Schreiber, Ryan L. Muetzel, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Loes M. Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Irene Pappa, Lukas Pirpamer, Sara Pudas, Benno Pütz, Kumar B. Rajan, Adaikalavan Ramasamy, Jennifer S. Richards, Shannon L. Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Emma J. Rose, Natalie A. Royle, Tatjana Rundek, Philipp G. Sämann, Claudia L. Satizabal, Lianne Schmaal, Andrew J. Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V. Smith, Emma Sprooten, Lachlan T. Strike, Alexander Teumer, Russell Thomson, Diana Tordesillas-Gutierrez, Roberto Toro, Daniah Trabzuni, Dhananjay Vaidya, Jeroen Van der Grond, Dennis Van der Meer, Marjolein M. J. Van Donkelaar, Kristel R. Van Eijk, Theo G. M. Van Erp, Daan Van Rooij, Esther Walton, Lars T. Westlye, Christopher D. Whelan, Beverly G. Windham, Anderson M. Winkler, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Bing Xu, Lisa R. Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P. Zwiers, Ingrid Agartz, Neelum T. Aggarwal, Laura Almasy, David Ames, Philippe Amouyel, Ole A. Andreassen, Sampath Arepalli, Amelia A. Assareh, Sandra Barral, Mark E. Bastin, Diane M. Becker, James T. Becker, David A. Bennett, John Blangero, Hans van Bokhoven, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Kazima B. Bulayeva, Wiepke Cahn, Vince D. Calhoun, Dara M. Cannon, Gianpiero L. Cavalleri, Christopher Chen, Ching-Yu Cheng, Sven Cichon, Mark R. Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Eco J. C. De Geus, Philip L. De Jager, Greig I. de Zubicaray, Norman Delanty, Chantal Depondt, Anita L. DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Susanne Erk, Thomas Espeseth, Denis A. Evans, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra A. Fleischman, Ian Ford, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H. H. Göring, Hans J. Grabe, Robert C. Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G. Hernandez, Dirk J. Heslenfeld, Beng-Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Hilleke E. Hulshoff Pol, Masashi Ikeda, M. Kamran Ikram, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kloszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, W. T. Longstreth Jr, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Katie L. McMahon, Francis J. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Steven G. Potkin, Bruce M. Psaty, Simone Reppermund, Marcella Rietschel, Joshua L. Roffman, Nina Romanczuk-Seiferth, Jerome I. Rotter, Mina Ryten, Ralph L. Sacco, Perminder S. Sachdev, Andrew J. Saykin, Reinhold Schmidt, Peter R. Schofield, Sigurdur Sigurdsson, Andy Simmons, Andrew Singleton, Sanjay M. Sisodiya, Colin Smith, Jordan W. Smoller, Hilkka Soininen, Velandai Srikanth, Vidar M. Steen, David J. Stott, Jessika E. Sussmann, Anbupalam Thalamuthu, Henning Tiemeier, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Jessica A. Turner, Christophe Tzourio, Andre G. Uitterlinden, Maria C. Valdés Hernández, Marcel Van der Brug, Aad Van der Lugt, Nic J. A. Van der Wee, Cornelia M. Van Duijn, Neeltje E. M. Van Haren, Dennis Van ′t Ent, Marie-Jose Van Tol, Badri N. Vardarajan, Dick J. Veltman, Meike W. Vernooij, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Thomas H. Wassink, Michael E. Weale, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y. Wong, Clinton B. Wright, H. Ronald Zielke, Alan B. Zonderman, Ian J. Deary, Charles DeCarli, Helena Schmidt, Nicholas G. Martin, Anton J. M. De Craen, Margaret J. Wright, Lenore J. Launer, Gunter Schumann, Myriam Fornage, Barbara Franke, Stéphanie Debette, Sarah E. Medland, M. Arfan Ikram and Paul M. Thompson |
MARC
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| 245 | 1 | 0 | |a Novel genetic loci underlying human intracranial volume identified through genome-wide association |c Hieab H. H. Adams, Derrek P. Hibar, Vincent Chouraki, Jason L. Stein, Paul A. Nyquist, Miguel E. Rentería, Stella Trompet, Alejandro Arias-Vasquez, Sudha Seshadri, Sylvane Desrivières, Ashley H. Beecham, Neda Jahanshad, Katharina Wittfeld, Sven J. Van der Lee, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Alexa Beiser, Manon Bernard, Joshua C. Bis, Laura M. E. Blanken, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Ganesh Chauhan, Qiang Chen, Christopher R. K. Ching, Gabriel Cuellar-Partida, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Irina Filippi, Tian Ge, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, Corina U. Greven, Oliver Grimm, Michael E. Griswold, Tulio Guadalupe, Johanna Hass, Unn K. Haukvik, Saima Hilal, Edith Hofer, David Hoehn, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Dalia Kasperaviciute, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, Jiemin Liao, David C. M. Liewald, Lorna M. Lopez, Michelle Luciano, Christine Macare, Andre Marquand, Mar Matarin, Karen A. Mather, Manuel Mattheisen, Bernard Mazoyer, David R. McKay, Rebekah McWhirter, Yuri Milaneschi, Nazanin Mirza-Schreiber, Ryan L. Muetzel, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Loes M. Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Irene Pappa, Lukas Pirpamer, Sara Pudas, Benno Pütz, Kumar B. Rajan, Adaikalavan Ramasamy, Jennifer S. Richards, Shannon L. Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Emma J. Rose, Natalie A. Royle, Tatjana Rundek, Philipp G. Sämann, Claudia L. Satizabal, Lianne Schmaal, Andrew J. Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V. Smith, Emma Sprooten, Lachlan T. Strike, Alexander Teumer, Russell Thomson, Diana Tordesillas-Gutierrez, Roberto Toro, Daniah Trabzuni, Dhananjay Vaidya, Jeroen Van der Grond, Dennis Van der Meer, Marjolein M. J. Van Donkelaar, Kristel R. Van Eijk, Theo G. M. Van Erp, Daan Van Rooij, Esther Walton, Lars T. Westlye, Christopher D. Whelan, Beverly G. Windham, Anderson M. Winkler, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Bing Xu, Lisa R. Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P. Zwiers, Ingrid Agartz, Neelum T. Aggarwal, Laura Almasy, David Ames, Philippe Amouyel, Ole A. Andreassen, Sampath Arepalli, Amelia A. Assareh, Sandra Barral, Mark E. Bastin, Diane M. Becker, James T. Becker, David A. Bennett, John Blangero, Hans van Bokhoven, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Kazima B. Bulayeva, Wiepke Cahn, Vince D. Calhoun, Dara M. Cannon, Gianpiero L. Cavalleri, Christopher Chen, Ching-Yu Cheng, Sven Cichon, Mark R. Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Eco J. C. De Geus, Philip L. De Jager, Greig I. de Zubicaray, Norman Delanty, Chantal Depondt, Anita L. DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Susanne Erk, Thomas Espeseth, Denis A. Evans, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra A. Fleischman, Ian Ford, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H. H. Göring, Hans J. Grabe, Robert C. Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G. Hernandez, Dirk J. Heslenfeld, Beng-Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Hilleke E. Hulshoff Pol, Masashi Ikeda, M. Kamran Ikram, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kloszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, W. T. Longstreth Jr, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Katie L. McMahon, Francis J. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Steven G. Potkin, Bruce M. Psaty, Simone Reppermund, Marcella Rietschel, Joshua L. Roffman, Nina Romanczuk-Seiferth, Jerome I. Rotter, Mina Ryten, Ralph L. Sacco, Perminder S. Sachdev, Andrew J. Saykin, Reinhold Schmidt, Peter R. Schofield, Sigurdur Sigurdsson, Andy Simmons, Andrew Singleton, Sanjay M. Sisodiya, Colin Smith, Jordan W. Smoller, Hilkka Soininen, Velandai Srikanth, Vidar M. Steen, David J. Stott, Jessika E. Sussmann, Anbupalam Thalamuthu, Henning Tiemeier, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Jessica A. Turner, Christophe Tzourio, Andre G. Uitterlinden, Maria C. Valdés Hernández, Marcel Van der Brug, Aad Van der Lugt, Nic J. A. Van der Wee, Cornelia M. Van Duijn, Neeltje E. M. Van Haren, Dennis Van ′t Ent, Marie-Jose Van Tol, Badri N. Vardarajan, Dick J. Veltman, Meike W. Vernooij, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Thomas H. Wassink, Michael E. Weale, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y. Wong, Clinton B. Wright, H. Ronald Zielke, Alan B. Zonderman, Ian J. Deary, Charles DeCarli, Helena Schmidt, Nicholas G. Martin, Anton J. M. De Craen, Margaret J. Wright, Lenore J. Launer, Gunter Schumann, Myriam Fornage, Barbara Franke, Stéphanie Debette, Sarah E. Medland, M. Arfan Ikram and Paul M. Thompson |
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| 520 | |a Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (ρgenetic = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (Ncombined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits. | ||
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Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Eco J. C. De Geus, Philip L. De Jager, Greig I. de Zubicaray, Norman Delanty, Chantal Depondt, Anita L. DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Susanne Erk, Thomas Espeseth, Denis A. Evans, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra A. Fleischman, Ian Ford, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H. H. Göring, Hans J. Grabe, Robert C. Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G. Hernandez, Dirk J. Heslenfeld, Beng-Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Hilleke E. Hulshoff Pol, Masashi Ikeda, M. Kamran Ikram, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kloszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, W. T. Longstreth Jr, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Katie L. McMahon, Francis J. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. 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Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y. Wong, Clinton B. Wright, H. Ronald Zielke, Alan B. Zonderman, Ian J. Deary, Charles DeCarli, Helena Schmidt, Nicholas G. Martin, Anton J. M. De Craen, Margaret J. Wright, Lenore J. Launer, Gunter Schumann, Myriam Fornage, Barbara Franke, Stéphanie Debette, Sarah E. Medland, M. Arfan Ikram and Paul M. Thompson"]},"person":[{"role":"aut","given":"Hieab","display":"Adams, Hieab","family":"Adams"},{"display":"Krämer, Bernd","given":"Bernd","family":"Krämer","role":"aut"},{"role":"aut","display":"Gruber, Oliver","given":"Oliver","family":"Gruber"},{"family":"Meyer-Lindenberg","display":"Meyer-Lindenberg, Andreas","given":"Andreas","role":"aut"},{"role":"aut","family":"Rietschel","display":"Rietschel, Marcella","given":"Marcella"}],"language":["eng"],"title":[{"title":"Novel genetic loci underlying human intracranial volume identified through genome-wide association","title_sort":"Novel genetic loci underlying human intracranial volume identified through genome-wide association"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"id":{"doi":["10.1038/nn.4398"],"eki":["1588141969"]},"physDesc":[{"extent":"14 S."}],"relHost":[{"note":["Gesehen am 02.03.05"],"part":{"issue":"12","extent":"14","volume":"19","text":"19(2016), 12, Seite 1569-1582","pages":"1569-1582","year":"2016"},"id":{"eki":["303393823"],"zdb":["1494955-6"],"issn":["1546-1726"]},"physDesc":[{"extent":"Online-Ressource"}],"title":[{"title":"Nature neuroscience","title_sort":"Nature neuroscience"}],"origin":[{"publisher":"Nature America","dateIssuedDisp":"1998-","dateIssuedKey":"1998","publisherPlace":"New York, NY"}],"type":{"bibl":"periodical","media":"Online-Ressource"},"pubHistory":["1.1998 -"],"titleAlt":[{"title":"Neuroscience"}],"language":["eng"],"recId":"303393823","disp":"Novel genetic loci underlying human intracranial volume identified through genome-wide associationNature neuroscience"}],"note":["Gesehen am 26.02.2019"]} | ||
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