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Genetic variants associated with longitudinal changes in brain structure across the lifespan

Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, t...

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Main Authors: Brouwer, Rachel M. (Author) , Klein, Marieke (Author) , Grasby, Katrina L. (Author) , Schnack, Hugo G. (Author) , Jahanshad, Neda (Author) , Teeuw, Jalmar (Author) , Thomopoulos, Sophia I. (Author) , Sprooten, Emma (Author) , Franz, Carol E. (Author) , Gogtay, Nitin (Author) , Kremen, William S. (Author) , Panizzon, Matthew S. (Author) , Olde Loohuis, Loes M. (Author) , Whelan, Christopher D. (Author) , Aghajani, Moji (Author) , Alloza, Clara (Author) , Alnæs, Dag (Author) , Artiges, Eric (Author) , Ayesa-Arriola, Rosa (Author) , Barker, Gareth J. (Author) , Bastin, Mark E. (Author) , Blok, Elisabet (Author) , Bøen, Erlend (Author) , Breukelaar, Isabella A. (Author) , Bright, Joanna K. (Author) , Buimer, Elizabeth E. L. (Author) , Bülow, Robin (Author) , Cannon, Dara M. (Author) , Ciufolini, Simone (Author) , Crossley, Nicolas A. (Author) , Damatac, Christienne G. (Author) , Dazzan, Paola (Author) , de Mol, Casper L. (Author) , de Zwarte, Sonja M. C. (Author) , Desrivières, Sylvane (Author) , Díaz-Caneja, Covadonga M. (Author) , Doan, Nhat Trung (Author) , Dohm, Katharina (Author) , Fröhner, Juliane H. (Author) , Goltermann, Janik (Author) , Grigis, Antoine (Author) , Grotegerd, Dominik (Author) , Han, Laura K. M. (Author) , Harris, Mathew A. (Author) , Hartman, Catharina A. (Author) , Heany, Sarah J. (Author) , Heindel, Walter (Author) , Heslenfeld, Dirk J. (Author) , Hohmann, Sarah (Author) , Ittermann, Bernd (Author) , Jansen, Philip R. (Author) , Janssen, Joost (Author) , Jia, Tianye (Author) , Jiang, Jiyang (Author) , Jockwitz, Christiane (Author) , Karali, Temmuz (Author) , Keeser, Daniel (Author) , Koevoets, Martijn G. J. C. (Author) , Lenroot, Rhoshel K. (Author) , Malchow, Berend (Author) , Mandl, René C. W. (Author) , Medel, Vicente (Author) , Meinert, Susanne (Author) , Morgan, Catherine A. (Author) , Mühleisen, Thomas W. (Author) , Nabulsi, Leila (Author) , Opel, Nils (Author) , de la Foz, Víctor Ortiz-García (Author) , Overs, Bronwyn J. (Author) , Paillère Martinot, Marie-Laure (Author) , Redlich, Ronny (Author) , Marques, Tiago Reis (Author) , Repple, Jonathan (Author) , Roberts, Gloria (Author) , Roshchupkin, Gennady V. (Author) , Setiaman, Nikita (Author) , Shumskaya, Elena (Author) , Stein, Frederike (Author) , Sudre, Gustavo (Author) , Takahashi, Shun (Author) , Thalamuthu, Anbupalam (Author) , Tordesillas-Gutiérrez, Diana (Author) , van der Lugt, Aad (Author) , van Haren, Neeltje E. M. (Author) , Wardlaw, Joanna M. (Author) , Wen, Wei (Author) , Westeneng, Henk-Jan (Author) , Wittfeld, Katharina (Author) , Zhu, Alyssa H. (Author) , Zugman, Andre (Author) , Armstrong, Nicola J. (Author) , Bonfiglio, Gaia (Author) , Bralten, Janita (Author) , Dalvie, Shareefa (Author) , Davies, Gail (Author) , Di Forti, Marta (Author) , Ding, Linda (Author) , Donohoe, Gary (Author) , Forstner, Andreas J. (Author) , Gonzalez-Peñas, Javier (Author) , Guimaraes, Joao P. O. F. T. (Author) , Homuth, Georg (Author) , Hottenga, Jouke-Jan (Author) , Knol, Maria J. (Author) , Kwok, John B. J. (Author) , Le Hellard, Stephanie (Author) , Mather, Karen A. (Author) , Milaneschi, Yuri (Author) , Morris, Derek W. (Author) , Nöthen, Markus M. (Author) , Papiol, Sergi (Author) , Rietschel, Marcella (Author) , Santoro, Marcos L. (Author) , Steen, Vidar M. (Author) , Stein, Jason L. (Author) , Streit, Fabian (Author) , Tankard, Rick M. (Author) , Teumer, Alexander (Author) , van ‘t Ent, Dennis (Author) , van der Meer, Dennis (Author) , van Eijk, Kristel R. (Author) , Vassos, Evangelos (Author) , Vázquez-Bourgon, Javier (Author) , Witt, Stephanie (Author) , Adams, Hieab H. H. (Author) , Agartz, Ingrid (Author) , Ames, David (Author) , Amunts, Katrin (Author) , Andreassen, Ole A. (Author) , Arango, Celso (Author) , Banaschewski, Tobias (Author) , Baune, Bernhard T. (Author) , Belangero, Sintia I. (Author) , Bokde, Arun L. W. (Author) , Boomsma, Dorret I. (Author) , Bressan, Rodrigo A. (Author) , Brodaty, Henry (Author) , Buitelaar, Jan K. (Author) , Cahn, Wiepke (Author) , Caspers, Svenja (Author) , Cichon, Sven (Author) , Crespo-Facorro, Benedicto (Author) , Cox, Simon R. (Author) , Dannlowski, Udo (Author) , Elvsåshagen, Torbjørn (Author) , Espeseth, Thomas (Author) , Falkai, Peter G. (Author) , Fisher, Simon E. (Author) , Flor, Herta (Author) , Fullerton, Janice M. (Author) , Garavan, Hugh (Author) , Gowland, Penny A. (Author) , Grabe, Hans J. (Author) , Hahn, Tim (Author) , Heinz, Andreas (Author) , Hillegers, Manon (Author) , Hoare, Jacqueline (Author) , Hoekstra, Pieter J. (Author) , Ikram, Mohammad A. (Author) , Jackowski, Andrea P. (Author) , Jansen, Andreas (Author) , Jönsson, Erik G. (Author) , Kahn, Rene S. (Author) , Kircher, Tilo (Author) , Korgaonkar, Mayuresh S. (Author) , Krug, Axel (Author) , Lemaitre, Herve (Author) , Malt, Ulrik F. (Author) , Martinot, Jean-Luc (Author) , McDonald, Colm (Author) , Mitchell, Philip B. (Author) , Muetzel, Ryan L. (Author) , Murray, Robin M. (Author) , Nees, Frauke (Author) , Nenadić, Igor (Author) , Oosterlaan, Jaap (Author) , Ophoff, Roel A. (Author) , Pan, Pedro M. (Author) , Penninx, Brenda W. J. H. (Author) , Poustka, Luise (Author) , Sachdev, Perminder S. (Author) , Salum, Giovanni A. (Author) , Schofield, Peter R. (Author) , Schumann, Gunter (Author) , Shaw, Philip (Author) , Sim, Kang (Author) , Smolka, Michael N. (Author) , Stein, Dan J. (Author) , Trollor, Julian N. (Author) , van den Berg, Leonard H. (Author) , Veldink, Jan H. (Author) , Walter, Henrik (Author) , Westlye, Lars T. (Author) , Whelan, Robert (Author) , White, Tonya (Author) , Wright, Margaret J. (Author) , Medland, Sarah E. (Author) , Franke, Barbara (Author) , Thompson, Paul M. (Author) , Hulshoff Pol, Hilleke E. (Author)
Format: Article (Journal)
Language:English
Published: 05 April 2022
In: Nature neuroscience
Year: 2022, Volume: 25, Issue: 4, Pages: 421-432
ISSN:1546-1726
DOI:10.1038/s41593-022-01042-4
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41593-022-01042-4
Verlag, lizenzpflichtig, Volltext: http://www.nature.com/articles/s41593-022-01042-4
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Author Notes:Rachel M. Brouwer, Marieke Klein, Katrina L. Grasby, Hugo G. Schnack, Neda Jahanshad, Jalmar Teeuw, Sophia I. Thomopoulos, Emma Sprooten, Carol E. Franz, Nitin Gogtay, William S. Kremen, Matthew S. Panizzon, Loes M. Olde Loohuis, Christopher D. Whelan, Moji Aghajani, Clara Alloza, Dag Alnæs, Eric Artiges, Rosa Ayesa-Arriola, Gareth J. Barker, Mark E. Bastin, Elisabet Blok, Erlend Bøen, Isabella A. Breukelaar, Joanna K. Bright, Elizabeth E.L. Buimer, Robin Bülow, Dara M. Cannon, Simone Ciufolini, Nicolas A. Crossley, Christienne G. Damatac, Paola Dazzan, Casper L. de Mol, Sonja M. C. de Zwarte, Sylvane Desrivières, Covadonga M. Díaz-Caneja, Nhat Trung Doan, Katharina Dohm, Juliane H. Fröhner, Janik Goltermann, Antoine Grigis, Dominik Grotegerd, Laura K.M. Han, Mathew A. Harris, Catharina A. Hartman, Sarah J. Heany, Walter Heindel, Dirk J. Heslenfeld, Sarah Hohmann, Bernd Ittermann, Philip R. Jansen, Joost Janssen, Tianye Jia, Jiyang Jiang, Christiane Jockwitz, Temmuz Karali, Daniel Keeser, Martijn G.J.C. Koevoets, Rhoshel K. Lenroot, Berend Malchow, René C.W. Mandl, Vicente Medel, Susanne Meinert, Catherine A. Morgan, Thomas W. Mühleisen, Leila Nabulsi, Nils Opel, Víctor Ortiz-García de la Foz, Bronwyn J. Overs, Marie-Laure Paillère Martinot, Ronny Redlich, Tiago Reis Marques, Jonathan Repple, Gloria Roberts, Gennady V. Roshchupkin, Nikita Setiaman, Elena Shumskaya, Frederike Stein, Gustavo Sudre, Shun Takahashi, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Aad van der Lugt, Neeltje E.M. van Haren, Joanna M. Wardlaw, Wei Wen, Henk-Jan Westeneng, Katharina Wittfeld, Alyssa H. Zhu, Andre Zugman, Nicola J. Armstrong, Gaia Bonfiglio, Janita Bralten, Shareefa Dalvie, Gail Davies, Marta Di Forti, Linda Ding, Gary Donohoe, Andreas J. Forstner, Javier Gonzalez-Peñas, Joao P.O.F.T. Guimaraes, Georg Homuth, Jouke-Jan Hottenga, Maria J. Knol, John B.J. Kwok, Stephanie Le Hellard, Karen A. Mather, Yuri Milaneschi, Derek W. Morris, Markus M. Nöthen, Sergi Papiol, Marcella Rietschel, Marcos L. Santoro, Vidar M. Steen, Jason L. Stein, Fabian Streit, Rick M. Tankard, Alexander Teumer, Dennis van ‘t Ent, Dennis van der Meer, Kristel R. van Eijk, Evangelos Vassos, Javier Vázquez-Bourgon, Stephanie H. Witt, Hieab H.H. Adams, Ingrid Agartz, David Ames, Katrin Amunts, Ole A. Andreassen, Celso Arango, Tobias Banaschewski, Bernhard T. Baune, Sintia I. Belangero, Arun L.W. Bokde, Dorret I. Boomsma, Rodrigo A. Bressan, Henry Brodaty, Jan K. Buitelaar, Wiepke Cahn, Svenja Caspers, Sven Cichon, Benedicto Crespo-Facorro, Simon R. Cox, Udo Dannlowski, Torbjørn Elvsåshagen, Thomas Espeseth, Peter G. Falkai, Simon E. Fisher, Herta Flor, Janice M. Fullerton, Hugh Garavan, Penny A. Gowland, Hans J. Grabe, Tim Hahn, Andreas Heinz, Manon Hillegers, Jacqueline Hoare, Pieter J. Hoekstra, Mohammad A. Ikram, Andrea P. Jackowski, Andreas Jansen, Erik G. Jönsson, Rene S. Kahn, Tilo Kircher, Mayuresh S. Korgaonkar, Axel Krug, Herve Lemaitre, Ulrik F. Malt, Jean-Luc Martinot, Colm McDonald, Philip B. Mitchell, Ryan L. Muetzel, Robin M. Murray, Frauke Nees, Igor Nenadić, Jaap Oosterlaan, Roel A. Ophoff, Pedro M. Pan, Brenda W.J.H. Penninx, Luise Poustka, Perminder S. Sachdev, Giovanni A. Salum, Peter R. Schofield, Gunter Schumann, Philip Shaw, Kang Sim, Michael N. Smolka, Dan J. Stein, Julian N. Trollor, Leonard H. van den Berg, Jan H. Veldink, Henrik Walter, Lars T. Westlye, Robert Whelan, Tonya White, Margaret J. Wright, Sarah E. Medland, Barbara Franke, Paul M. Thompson and Hilleke E. Hulshoff Pol

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245 1 0 |a Genetic variants associated with longitudinal changes in brain structure across the lifespan  |c Rachel M. Brouwer, Marieke Klein, Katrina L. Grasby, Hugo G. Schnack, Neda Jahanshad, Jalmar Teeuw, Sophia I. Thomopoulos, Emma Sprooten, Carol E. Franz, Nitin Gogtay, William S. Kremen, Matthew S. Panizzon, Loes M. Olde Loohuis, Christopher D. Whelan, Moji Aghajani, Clara Alloza, Dag Alnæs, Eric Artiges, Rosa Ayesa-Arriola, Gareth J. Barker, Mark E. Bastin, Elisabet Blok, Erlend Bøen, Isabella A. Breukelaar, Joanna K. Bright, Elizabeth E.L. Buimer, Robin Bülow, Dara M. Cannon, Simone Ciufolini, Nicolas A. Crossley, Christienne G. Damatac, Paola Dazzan, Casper L. de Mol, Sonja M. C. de Zwarte, Sylvane Desrivières, Covadonga M. Díaz-Caneja, Nhat Trung Doan, Katharina Dohm, Juliane H. Fröhner, Janik Goltermann, Antoine Grigis, Dominik Grotegerd, Laura K.M. Han, Mathew A. Harris, Catharina A. Hartman, Sarah J. Heany, Walter Heindel, Dirk J. Heslenfeld, Sarah Hohmann, Bernd Ittermann, Philip R. Jansen, Joost Janssen, Tianye Jia, Jiyang Jiang, Christiane Jockwitz, Temmuz Karali, Daniel Keeser, Martijn G.J.C. Koevoets, Rhoshel K. Lenroot, Berend Malchow, René C.W. Mandl, Vicente Medel, Susanne Meinert, Catherine A. Morgan, Thomas W. Mühleisen, Leila Nabulsi, Nils Opel, Víctor Ortiz-García de la Foz, Bronwyn J. Overs, Marie-Laure Paillère Martinot, Ronny Redlich, Tiago Reis Marques, Jonathan Repple, Gloria Roberts, Gennady V. Roshchupkin, Nikita Setiaman, Elena Shumskaya, Frederike Stein, Gustavo Sudre, Shun Takahashi, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Aad van der Lugt, Neeltje E.M. van Haren, Joanna M. Wardlaw, Wei Wen, Henk-Jan Westeneng, Katharina Wittfeld, Alyssa H. Zhu, Andre Zugman, Nicola J. Armstrong, Gaia Bonfiglio, Janita Bralten, Shareefa Dalvie, Gail Davies, Marta Di Forti, Linda Ding, Gary Donohoe, Andreas J. Forstner, Javier Gonzalez-Peñas, Joao P.O.F.T. Guimaraes, Georg Homuth, Jouke-Jan Hottenga, Maria J. Knol, John B.J. Kwok, Stephanie Le Hellard, Karen A. Mather, Yuri Milaneschi, Derek W. Morris, Markus M. Nöthen, Sergi Papiol, Marcella Rietschel, Marcos L. Santoro, Vidar M. Steen, Jason L. Stein, Fabian Streit, Rick M. Tankard, Alexander Teumer, Dennis van ‘t Ent, Dennis van der Meer, Kristel R. van Eijk, Evangelos Vassos, Javier Vázquez-Bourgon, Stephanie H. Witt, Hieab H.H. Adams, Ingrid Agartz, David Ames, Katrin Amunts, Ole A. Andreassen, Celso Arango, Tobias Banaschewski, Bernhard T. Baune, Sintia I. Belangero, Arun L.W. Bokde, Dorret I. Boomsma, Rodrigo A. Bressan, Henry Brodaty, Jan K. Buitelaar, Wiepke Cahn, Svenja Caspers, Sven Cichon, Benedicto Crespo-Facorro, Simon R. Cox, Udo Dannlowski, Torbjørn Elvsåshagen, Thomas Espeseth, Peter G. Falkai, Simon E. Fisher, Herta Flor, Janice M. Fullerton, Hugh Garavan, Penny A. Gowland, Hans J. Grabe, Tim Hahn, Andreas Heinz, Manon Hillegers, Jacqueline Hoare, Pieter J. Hoekstra, Mohammad A. Ikram, Andrea P. Jackowski, Andreas Jansen, Erik G. Jönsson, Rene S. Kahn, Tilo Kircher, Mayuresh S. Korgaonkar, Axel Krug, Herve Lemaitre, Ulrik F. Malt, Jean-Luc Martinot, Colm McDonald, Philip B. Mitchell, Ryan L. Muetzel, Robin M. Murray, Frauke Nees, Igor Nenadić, Jaap Oosterlaan, Roel A. Ophoff, Pedro M. Pan, Brenda W.J.H. Penninx, Luise Poustka, Perminder S. Sachdev, Giovanni A. Salum, Peter R. Schofield, Gunter Schumann, Philip Shaw, Kang Sim, Michael N. Smolka, Dan J. Stein, Julian N. Trollor, Leonard H. van den Berg, Jan H. Veldink, Henrik Walter, Lars T. Westlye, Robert Whelan, Tonya White, Margaret J. Wright, Sarah E. Medland, Barbara Franke, Paul M. Thompson and Hilleke E. Hulshoff Pol 
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520 |a Human brain structure changes throughout the lifespan. Altered brain growth or rates of decline are implicated in a vast range of psychiatric, developmental and neurodegenerative diseases. In this study, we identified common genetic variants that affect rates of brain growth or atrophy in what is, to our knowledge, the first genome-wide association meta-analysis of changes in brain morphology across the lifespan. Longitudinal magnetic resonance imaging data from 15,640 individuals were used to compute rates of change for 15 brain structures. The most robustly identified genes GPR139, DACH1 and APOE are associated with metabolic processes. We demonstrate global genetic overlap with depression, schizophrenia, cognitive functioning, insomnia, height, body mass index and smoking. Gene set findings implicate both early brain development and neurodegenerative processes in the rates of brain changes. Identifying variants involved in structural brain changes may help to determine biological pathways underlying optimal and dysfunctional brain development and aging. 
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SRT |a BROUWERRACGENETICVAR0520 

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