Abstract

Cortical thickness, surface area and volumes (MRI cortical measures) vary with age and cognitive function, and in neurological and psychiatric diseases. We examined heritability, genetic correlations and genome-wide associations of cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprised 22,822 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the United Kingdom Biobank. Significant associations were replicated in the Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium, and their biological implications explored using bioinformatic annotation and pathway analyses. We identified genetic heterogeneity between cortical measures and brain regions, and 161 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There was 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

September 9, 2018

Authors

Edith Hofer, Gennady V Roshchupkin, Hieab HH 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 van der 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 Amouye, 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, ENIGMA consortium, Katrina L Grasby, Neda Jahanshad, Jodie N Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P Hibar, Penelope A Lind, Fabrizio Pizzagalli, RK Ching Christopher, B McMahon Mary Agnes, Natalia Shatokhina, Leo CP Zsembik, Ingrid Agartz, Saud Alhusaini, Marcio AA Almeida, Dag Alnæs, Inge K Amlien, Micael Andersson, Tyler Ard, Nicola J Armstrong, Allison Ashley-Koch, Manon Bernard, Rachel M Brouwer, Elizabeth EL Buimer, Robin Bülow, Christian Bürger, Dara M Cannon, Mallar Chakravarty, Qiang Chen, Joshua W Cheung, Baptiste Couvy-Duchesne, Anders M Dale, Shareefa Dalvie, Tânia K de Araujo, Greig I de Zubicaray, Sonja MC de Zwarte, Anouk den Braber, Nhat Trung Doan, Katharina Dohm, Stefan Ehrlich, Hannah-Ruth Engelbrecht, Susanne Erk, Chun Chieh Fan, Iryna O Fedko, Sonya F Foley, Judith M Ford, Masaki Fukunaga, Melanie E Garrett, Tian Ge, Sudheer Giddaluru, Aaron L Goldman, Nynke A Groenewold, Dominik Grotegerd, Tiril P Gurholt, Boris A Gutman, Narelle K Hansell, Mathew A Harris, Marc B Harrison, Courtney C Haswell, Michael Hauser, Stefan Herms, Dirk J Heslenfeld, New Fei Ho, David Hoehn

Journal

BioRxiv

Pages

409649

Publisher

Cold Spring Harbor Laboratory