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Mapping Cortical Brain Asymmetry in 17,141 Healthy Individuals Worldwide via the ENIGMA Consortium

By Xiang-Zhen Kong, Samuel R Mathias, Tulio Guadalupe, Christoph Abé, Ingrid Agartz, Theophilus N. Akudjedu, Aleman Andre, Alhusaini Saud, Nicholas B. Allen, David Ames, Ole A Andreassen, Alejandro Arias Vasquez, Nicola J. Armstrong, Felipe Bergo, Mark E Bastin, Albert Batalla, Jochen Bauer, Bernhard T. Baune, Ramona Baur, Joseph Biederman, Sara K. Blaine, Premika Boedhoe, Erlend Bøen, Anushree Bose, Janita Bralten, Daniel Brandeis, Silvia Brem, Henry Brodaty, Henrieke Bröhl, Samantha J. Brooks, Jan Buitelaar, Christian Bürger, Robin Bülow, Vince Calhoun, Anna Calvo, Erick Jorge Canales-Rodríguez, Jose M. Canive, Dara M. Cannon, Elisabeth C. Caparelli, Francisco X. Castellanos, Gianpiero L. Cavalleri, Fernando Cendes, Tiffany Moukbel Chaim-Avancini, Kaylita Chantiluke, Qun-lin Chen, Xiayu Chen, Yuqi Cheng, Anastasia Christakou, Vincent P. Clark, David Coghill, Colm G. Connolly, Annette Conzelmann, Aldo Cόrdova-Palomera, Janna Cousijn, Tim Crow, Ana Cubillo, Udo Dannlowski, Sara Ambrosino de Bruttopilo, Patrick de Zeeuw, Ian J Deary, Norman Delanty, Damion V. Demeter, Adriana Di Martino, Erin W Dickie, Bruno Dietsche, N. Trung Doan, Colin P. Doherty, Alysa Doyle, Sarah Durston, Eric Earl, Stefan Ehrlich, Carl Johan Ekman, Torbjørn Elvsåshagen, Jeffery N. Epstein, Damien A. Fair, Stephen Faraone, Helena Fatouros-Bergman, Guillen Fernndez, Geraldo Busatto Filho, Lena Flyckt, Katharina Forster, Fouche Jean-Paul, John J. Foxe, Paola Fuentes-Claramonte, Janice Fullerton, Hugh Garavan, Danielle do Santos Garcia, Ian H. Gotlib, Anna E. Goudriaan, Hans Jorgen Grabe, Nynke A. Groenewold, Dominik Grotegerd, Oliver Gruber, Tiril Gurholt, Jan Haavik, Tim Hahn, Narelle K. Hansell, Mathew A Harris, Catharina Hartman, Maria del Carmen Valdes Hernandez, Dirk Heslenfeld, Robert Hester, Derrek Paul Hibar, Beng-Choon Ho, Tiffany C. Ho, Pieter J. Hoekstra, Ruth J. van Holst, Martine Hoogman, Marie F. Hovik, Fleur M. Howells, Kenneth Hugdahl, Chaim Huyser, Martind Ingvar, Lourdes Irwin, Akari Ishikawa, Anthony James, Neda Jahanshad, Terry L Jernigan, Erik G Jonsson, Claas Kahler, Vasily Kaleda, Clare Kelly, Michael Kerich, Matcheri S Keshavan, Sabin Khadka, Tilo Kircher, Gregor Kohls, Kerstin Konrad, Ozlem Korucuoglu, Bernd Kramer, Axel Krug, Jun Soo Kwon, Nanda Lambregts-Rommelse, Mikael Landen, Luisa Lazaro, Irina Lebedeva, Rhoshel Lenroot, Klaus-Peter Lesch, Qinqin Li, Kelvin O. Lim, Jia Liu, Christine Lochner, Edythe D. London, Vera Lonning, Valentina Lorenzetti, Michelle Luciano, Maartje Luijten, Astri J. Lundervold, Scott Mackey, Frank P. MacMaster, Sophie Maingault, Charles B Malpas, Ulrik F. Malt, David Mataix-Cols, Rocio Martin-Santos, Andrew R. Mayer, Hazel McCarthy, Philip B Mitchell, Bryon A. Mueller, Susana Munoz Maniega, Bernard Mazoyer, Colm McDonald, Quinn McLellan, Katie L. McMahon, Genevieve McPhilemy, Reza Momenan, Angelica M. Morales, Janardhanan C. Narayanaswamy, Jose Carlos Vasques Moreira, Stener Nerland, Liam Nestor, Joel T. Nigg, Jan-Egil Nordvik, Stephanie Novotny, Eileen Oberwelland, Ruth L. O'Gorman, Jaap Oosterlaan, Bob Oranje, Catherine Orr, Bronwyn Overs, Paul Pauli, Martin Paulus, Kerstin Plessen, Georg G. von Polier, Edith Pomarol-Clotet, Jiang Qiu, Joaquim Radua, Josep Antoni Ramos-Quiroga, Y.C. Janardhan Reddy, Andreas Reif, Gloria Roberts, Pedro Rosa, Katya Rubia, Matthew D. Sacchet, Perminder S. Sachdev, Raymond Salvador, Lianne Schmaal, Lisanne Schweren, Larry Seidman, Jochen Seitz, Mauricio Henriques Serpa, Philip Shaw, Elena Shumskaya, Timothy J. Silk, Alan N. Simmons, Egle Simulionyte, Rajita Sinha, Zsuzsika Sjoerds, Runar Elle Smelror, Joan Carlos Soliva, Nadia Solowij, Scott R. Sponheim, Dan J. Stein, Elliot A Stein, Michael Stevens, Lachlan T. Strike, Gustavo Sudre, Jing Sui, Leanne Tamm, Hendrik S. Temmingh, Robert J. Thoma, Alexander Tomyshev, Giulia Tronchin, Jessica Turner, Anne Uhlmann, Theo G.M. van Erp, Odile van den Heuvel, Dennis van der Meer, Liza van Eijk, Alasdair Vance, Ilya M. Veer, Dick J. Veltman, Ganesan Venkatasubramanian, Oscar Vilarroya, Yolanda Vives-Gilabert, Aristotle N. Voineskos, Henry Volzke, Daniella Vuletic, Susanne Walitza, Henrik Walter, Esther Walton, Joanna M Wardlaw, Wei Wen, Lars T. Westlye, Christopher D. Whelan, Tonya White, Reinout W. Wiers, Margaret J Wright, Katharina Wittfeld, Tony T. Yang, Clarissa L. Yasuda, Yuliya Yoncheva, Murat Yucel, Je-Yeon Yun, Marcus Vinicius Zanetti, Zonglei Zhen, Xing-xing Zhu, Georg C. Ziegler, Kathrin Zierhut, Greig I. de Zubicaray, Marcel Zwiers, Karolinska Schizophrenia Project KaSP, David C Glahn, Barbara Franke, Fabrice Crivello, Nathalie Tzourio-Mazoyer, Simon E. Fisher, Paul M Thompson, Clyde Francks, Lars Farde, Goran Engberg, Sophie Erhardt, Simon Cervenka, Lilly Schwieler, Fredrik Piehl, Karin Collste, Pauliina Victorsson, Anna Malmqvist, Mikael Hedberg, Funda Orhan

Posted 01 Oct 2017
bioRxiv DOI: 10.1101/196634 (published DOI: 10.1073/pnas.1718418115)

Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.

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