Genetic determinants of cortical structure (thickness, surface area and 
volumes) among disease free adults in the CHARGE Consortium

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

doi:10.1101/409649

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Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium

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Witte, A. Veronica
External Organizations;
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Beyer, Frauke
External Organizations;
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Villringer, Arno
External Organizations;
Department Neurology, MPI for Human Cognitive and Brain Sciences, Max Planck Society;

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Citation

Hofer, E., Roshchupkin, G. V., Adams, H. H. H., Knol, M. J., Lin, H., Li, S., et al. (2019). Genetic determinants of cortical structure (thickness, surface area and volumes) among disease free adults in the CHARGE Consortium. bioRxiv. doi:10.1101/409649.

Cite as: https://hdl.handle.net/21.11116/0000-0004-D554-D

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 22,824 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 160 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.