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Genetic Determinants of Cortical Structure (Thickness, Surface Area and Volumes) among Disease Free Adults in the CHARGE Consortium

By Edith Hofer, Gennady V Roshchupkin, Hieab Adams, Maria Knol, Honghuang Lin, Shuo Li, Habil Zare, Shahzad Ahmad, Nicola Armstrong, Claudia Satizabal, Manon Bernard, Joshua Bis, Nathan Gillespie, Michelle Luciano, Aniket Mishra, Markus Scholz, Alexander Teumer, Rui Xia, Xueqiu Jian, Thomas Mosley, Yasaman Saba, Lukas Pirpamer, Stephan Seiler, James Becker, Owen Carmichael, Jerome Rotter, Bruce Psaty, Oscar Lopez, Najaf Amin, Sven Lee, Qiong Yang, Jayandra Himali, Pauline Maillard, Alexa Beiser, Charles DeCarli, Sherif Karama, Lindsay Lewis, Mark Bastin, Mat Harris, Ian Deary, Veronica Witte, Frauke Beyer, Markus Loeffler, Karen Mather, Peter Schofield, Anbupalam Thalamuthu, John Kwok, Margaret Wright, David Ames, Julian Trollor, Jiyang Jiang, Henry Brodaty, Wei Wen, Meike Vernooij, Albert Hofman, Andre Uitterlinden, Wiro Niessen, Katharina Wittfeld, Robin Bulow, Uwe Volker, Zdenka Pausova, Bruce Pike, Sophie Maingault, Fabrice Crivello, Christophe Tzourio, Philippe Amouyel, Bernard Mazoyer, Michael Neale, Carol Franz, Michael Lyons, Matthew Panizzon, Ole Andreassen, Anders Dale, Mark Logue, Katrina Grasby, Neda Jahanshad, Jodie Painter, Lucia Colodro-Conde, Janita Bralten, Derrek Hibar, Penelope Lind, Fabrizio Pizzagalli, Jason Stein, Paul Thompson, Sarah Medland, Perminder Sachdev, William Kremen, Joanna Wardlaw, Arno Villringer, Cornelia Duijn, Hans J J Grabe, William Longstreth, Myriam Fornage, Tomas Paus, Stephanie Debette, Arfan Ikram, Helena Schmidt, Reinhold Schmidt, Sudha Seshadri

Posted 09 Sep 2018
bioRxiv DOI: 10.1101/409649

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/beta-catenin, TGF-beta; 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.

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