Abstract

The radial unit hypothesis provides a framework for global (proliferation) and regional (distribution) expansion of the primate cerebral cortex. Using principal component analysis (PCA), we have identified cortical regions with shared variance in their surface area and cortical thickness, respectively, segmented from magnetic resonance images obtained in 23,800 participants. We then carried out meta-analyses of genome-wide association studies of the first two principal components for each phenotype. For surface area (but not cortical thickness), we have detected strong associations between each of the components and single nucleotide polymorphisms in a number of gene loci. The first (global) component was associated mainly with loci on chromosome 17 (9.5e-32 ≤ p ≤ 2.8e-10), including those detected previously as linked with intracranial volume and/or general cognitive function. The second (regional) component captured shared variation in the surface area of the primary and adjacent secondary visual cortices and showed a robust association with polymorphisms in a locus on chromosome 14 containing Disheveled Associated Activator of Morphogenesis 1 (DAAM1; p=2.4e-34). DAAM1 is a key component in the planar-cell-polarity signaling pathway. In follow-up studies, we have focused on the latter finding and established that: (1) DAAM1 is highly expressed between 12th and 22nd post-conception weeks in the human cerebral cortex; (2) genes co-expressed with DAAM1 in the primary visual cortex are enriched in mitochondria-related pathways; and (3) volume of the lateral geniculate nucleus, which projects to regions of the visual …

Date

2018

Authors

Jean Shin, Shaojie Ma, Edith Hofer, Yash Patel, Gennady V Roshchupkin, Andre M Sousa, Xueqiu Jian, Rebecca Gottesman, Thomas H Mosley, Myriam Fornage, Yasaman Saba, Lukas Pirpamer, Reinhold Schmidt, Helena Schmidt, Amaia Carrion-Castillo, Fabrice Crivello, Bernard Mazoyer, Joshua C Bis, Shuo Li, Qiong Yang, Michelle Luciano, Sherif Karama, Lindsay Lewis, Mark Bastin, Mathew A Harris, Joanna M Wardlaw, Ian E Deary, Markus Scholz, Markus Loeffler, Veronica Witte, Frauke Beyer, Arno Villringer, Nicola J Armstrong, Karen A Mather, David Ames, Jiyang Jiang, John B Kwok, Peter R Schofield, Anbupalam Thalamuthu, Julian N Trollor, Margaret J Wright, Henry Brodaty, Wei Wen, Perminder S Sachdev, Natalie Terzikhan, Tavia E Evans, Hieab HHH Adams, M Arfan Ikram, Stefan Frenzel, Sandra van der Auwera-Palitschka, Katharina Wittfeld, Robin Bülow, Hans Jörgen Grabe, Christophe Tzourio, Aniket Mishra, Sophie Maingault, Stephanie Debette, Nathan A Gillespie, Carol E Franz, William S Kremen, Linda Ding, Neda Jahanshad, ENIGMA Consortium, Nenad Sestan, Zdenka Pausova, Sudha Seshadri, Tomas Paus, neuroCHARGE Working Group, Katrina L Grasby, Neda Jahanshad, Jodie N Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P Hibar, Penelope A Lind, Fabrizio Pizzagalli, Christopher RK Ching, Mary Agnes B McMahon, Natalia Shatokhina, Leo 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, Mallasr 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, Dirk J Heslenfeld, David Hoehn, Laurena Holleran, Martine Hoogman, Jouke-Jan Hottenga, Masashi Ikeda, Deborah Janowitz, Iris E Jansen, Tianye Jia, Christiane Jockwitz, Ryota Kanai, Sherif Karama, Dalia Kasperaviciute, Tobias Kaufmann, Sinead Kelly, Masataka Kikuchi, Marieke Klein, Michael Knapp, Annchen R Knodt, Bernd Krämer, Thomas M Lancaster, Phil H Lee

Journal

bioRxiv

Pages

404558

Publisher

Cold Spring Harbor Laboratory