Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Edith Hofer, Gennady V. Roshchupkin, Hieab H. H. Adams, Maria J. Knol, Honghuang Lin, Shuo Li, Habil Zare, Shahzad Ahmad, Nicola J. Armstrong, Claudia L. Satizabal, Manon Bernard, Joshua C. Bis, Nathan A. Gillespie, Michelle Luciano, Aniket Mishra, Markus Scholz, Alexander Teumer, Rui Xia, Xueqiu Jian, Thomas H. Mosley, Yasaman Saba, Lukas Pirpamer, Stephan Seiler, James T. Becker, Owen Carmichael, Jerome I. Rotter, Bruce M. Psaty, Oscar L. Lopez, Najaf Amin, Sven J. Lee, Qiong Yang, Jayandra J. Himali, Pauline Maillard, Alexa S. Beiser, Charles DeCarli, Sherif Karama, Lindsay Lewis, Mat Harris, Mark E. Bastin, Ian J. Deary, A. Veronica Witte, Frauke Beyer, Markus Loeffler, Karen A. Mather, Peter R. Schofield, Anbupalam Thalamuthu, John B. Kwok, Margaret J. Wright, David Ames, Julian Trollor, Jiyang Jiang, Henry Brodaty, Wei Wen, Meike W. Vernooij, Albert Hofman, André G. Uitterlinden, Wiro J. Niessen, Katharina Wittfeld, Robin Bülow, Uwe Völker, Zdenka Pausova, G. Bruce Pike, Sophie Maingault, Fabrice Crivello, Christophe Tzourio, Philippe Amouyel, Bernard Mazoyer, Michael C. Neale, Carol E. Franz, Michael J. Lyons, Matthew S. Panizzon, Ole A. Andreassen, Anders M. Dale, Mark Logue, Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Jason L. Stein, Paul M. Thompson, Sarah E. Medland, Perminder S. Sachdev, William S. Kremen, Joanna M. Wardlaw, Arno Villringer, Cornelia M. Duijn, Hans J. Grabe, William T. Longstreth, Myriam Fornage, Tomas Paus, Stephanie Debette, M. Arfan Ikram, Helena Schmidt, Reinhold Schmidt () and Sudha Seshadri ()
Additional contact information
Edith Hofer: Medical University of Graz
Gennady V. Roshchupkin: Erasmus MC
Hieab H. H. Adams: Erasmus MC
Maria J. Knol: Erasmus MC
Honghuang Lin: Boston University School of Medicine
Shuo Li: Boston University School of Public Health
Habil Zare: Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio
Shahzad Ahmad: Erasmus MC
Nicola J. Armstrong: Mathematics and Statistics, Murdoch University
Claudia L. Satizabal: Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio
Manon Bernard: Hospital for Sick Children
Joshua C. Bis: University of Washington
Nathan A. Gillespie: Virginia Commonwealth University
Michelle Luciano: University of Edinburgh
Aniket Mishra: University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219
Markus Scholz: University of Leipzig
Alexander Teumer: University Medicine Greifswald
Rui Xia: University of Texas Health Science Center at Houston
Xueqiu Jian: University of Texas Health Science Center at Houston
Thomas H. Mosley: University of Mississippi Medical Center
Yasaman Saba: Medical University of Graz
Lukas Pirpamer: Medical University of Graz
Stephan Seiler: University of California-Davis
James T. Becker: University of Pittsburgh
Owen Carmichael: Pennington Biomedical Research Center
Jerome I. Rotter: Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center
Bruce M. Psaty: University of Washington
Oscar L. Lopez: University of Pittsburgh
Najaf Amin: Erasmus MC
Sven J. Lee: Erasmus MC
Qiong Yang: Boston University School of Public Health
Jayandra J. Himali: Boston University School of Public Health
Pauline Maillard: University of California-Davis
Alexa S. Beiser: Boston University School of Public Health
Charles DeCarli: University of California-Davis
Sherif Karama: McGill University, Montreal Neurological Institute
Lindsay Lewis: McGill University, Montreal Neurological Institute
Mat Harris: University of Edinburgh
Mark E. Bastin: University of Edinburgh
Ian J. Deary: University of Edinburgh
A. Veronica Witte: Max Planck Institute for Human Cognitive and Brain Sciences
Frauke Beyer: Max Planck Institute for Human Cognitive and Brain Sciences
Markus Loeffler: University of Leipzig
Karen A. Mather: University of New South Wales
Peter R. Schofield: Neuroscience Research Australia
Anbupalam Thalamuthu: University of New South Wales
John B. Kwok: University of New South Wales
Margaret J. Wright: The University of Queensland
David Ames: Royal Melbourne Hospital
Julian Trollor: University of New South Wales
Jiyang Jiang: University of New South Wales
Henry Brodaty: University of New South Wales
Wei Wen: University of New South Wales
Meike W. Vernooij: Erasmus MC
Albert Hofman: Erasmus MC
André G. Uitterlinden: Erasmus MC
Wiro J. Niessen: Erasmus MC
Katharina Wittfeld: German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald
Robin Bülow: University Medicine Greifswald
Uwe Völker: University Medicine Greifswald
Zdenka Pausova: Hospital for Sick Children
G. Bruce Pike: University of Calgary
Sophie Maingault: University of Bordeaux
Fabrice Crivello: University of Bordeaux
Christophe Tzourio: University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219
Philippe Amouyel: Centre Hospitalier Universitaire de Bordeaux, France; Inserm U1167
Bernard Mazoyer: University of Bordeaux
Michael C. Neale: Virginia Commonwealth University
Carol E. Franz: University of California San Diego
Michael J. Lyons: Boston University
Matthew S. Panizzon: University of California San Diego
Ole A. Andreassen: University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital
Anders M. Dale: University of California, San Diego
Mark Logue: Boston University School of Public Health
Katrina L. Grasby: Psychiatric Genetics, QIMR Berghofer Medical Research Institute
Neda Jahanshad: University of Southern California
Jodie N. Painter: Psychiatric Genetics, QIMR Berghofer Medical Research Institute
Lucía Colodro-Conde: Psychiatric Genetics, QIMR Berghofer Medical Research Institute
Janita Bralten: Radboud university medical center
Derrek P. Hibar: University of Southern California
Penelope A. Lind: Psychiatric Genetics, QIMR Berghofer Medical Research Institute
Fabrizio Pizzagalli: University of Southern California
Jason L. Stein: University of North Carolina at Chapel Hill
Paul M. Thompson: University of Southern California
Sarah E. Medland: Psychiatric Genetics, QIMR Berghofer Medical Research Institute
Perminder S. Sachdev: University of New South Wales
William S. Kremen: University of California San Diego
Joanna M. Wardlaw: University of Edinburgh
Arno Villringer: Max Planck Institute for Human Cognitive and Brain Sciences
Cornelia M. Duijn: Erasmus MC
Hans J. Grabe: German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald
William T. Longstreth: University of Washington
Myriam Fornage: University of Texas Health Science Center at Houston
Tomas Paus: Holland Bloorview Kids Rehabilitation Hospital
Stephanie Debette: Boston University School of Medicine
M. Arfan Ikram: Erasmus MC
Helena Schmidt: Medical University of Graz
Reinhold Schmidt: Medical University of Graz
Sudha Seshadri: Glenn Biggs Institute for Alzheimer’s and Neurodegenerative Diseases, UT Health San Antonio

Nature Communications, 2020, vol. 11, issue 1, 1-16

Abstract: Abstract Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

Date: 2020
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DOI: 10.1038/s41467-020-18367-y

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