Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

All 166 authors (show less):
Theo G. M. vanErp, Odile A. van Den Heuvel, Christopher D. Whelan, Marcel P. Zwiers, Samuel R. Mathias, Yoshinari Abe, Lucija Abramovic, Tulio Guadalupe, Ingrid Agartz, Ole A. Andreassen, Alejandro Arias-Vasquez, Benjamin S. Aribisala, Nicola J. Armstrong, Volker Arolt, Eric Artiges, Rosa Ayesa-Arriola, Greig I. de Zubicaray, Vatche G. Baboyan, Sonja M. C. de Zwarte, Tobias Banaschewski, Gareth Barker, Mark E. Bastin, Bernhard T. Baune, John Blangero, Arun L. W. Bokde, Premika S. W. Boedhoe, Anushree Bose, Silvia Brem, Henry Brodaty, Uli Bromberg, Samantha Brooks, Christian Büchel, Vince D. Calhoun, Jan K. Buitelaar, Dara M. Cannon, Anna Cattrell, Yuqi Cheng, Christian Buchel, Patricia J. Conrod, Annette Conzelmann, Aiden Corvin, Benedicto Crespo-Facorro, Fabrice Crivello, Udo Dannlowski, Ian J. Deary, Sylvane Desrivières, Nhat Trung Doan, Gary Donohoe, Erlend S. Dørum, Stefan Ehrlich, Thomas Espeseth, Guillén S. E. Fernández, Masaki Fukunaga, Jürgen Gallinat, Hugh Garavan, Herta Flor, Michael Gill, Andrea Gonzalez Suarez, Penny Gowland, Hugh Hu, Hans J. Grabe, Dominik Grotegerd, Jean-Paul Fouche, Oliver Gruber, Saskia Hagenaars, Ryota Hashimoto, Tobias U. Hauser, Andreas Heinz, Neeltje E. M . van Haren, Derrek P. Hibar, Vincent Frouin, Pieter J. Hoekstra, Martine Hoogman, Fleur M. Howells, Hao Hu, Hilleke E. Hulshoff Pol, Chaim Huyser, Bernd Ittermann, Robert Whelan, Thomas Wolfers, Neda Jahanshad, Katharina Wittfeld, Erik G. Jönsson, Margaret J. Wright, Sarah Jurk, Jian Xu, Rene S. Kahn, Xiufeng Xu, Sinead Kelly, Je-Yeon Yun, JingJing J. Zhao, Bernd Kraemer, Erik G. Joensson, Harald Kugel, Jun Soo Kwon, Herve Lemaitre, Klaus-Peter Lesch, Christine Lochner, Michelle Luciano, Andre F. Marquand, Nicholas G. Martin, Ignacio Martínez-Zalacaín, Jean-Luc Martinot, David Mataix-Cols, Karen Mather, Colm McDonald, Ignacio Martinez-Zalacain, Katie L. McMahon, Sarah E. Medland, José M. Menchón, Derek W. Morris, Omar Mothersill, Susana Munoz Maniega, Benson Mwangi, Takashi Nakamae, Tomohiro Nakao, Janardhanan C. Narayanaswaamy, Frauke Nees, Jan E. Nordvik, A. Marten H. Onnink, Nils Opel, Roel Ophoff, Marie-Laure Paillère Martinot, Dimitri Papadopoulos Orfanos, Paul Pauli, Tomáš Paus, Luise Poustka, Janardhan Yc-C. Reddy, Miguel E. Renteria, Roberto Roiz-Santiáñez, Annerine Roos, Natalie A. Royle, Perminder Sachdev, Pascual Sánchez-Juan, Lianne Schmaal, Gunter Schumann, Elena Shumskaya, Michael N. Smolka, Pascual Sanchez-Juan, Jair C. Soares, Carles Soriano-Mas, Dan J. Stein, Lachlan T. Strike, Roberto Toro, Dennis van der Meer, Jessica A. Turner, Nathalie Tzourio-Mazoyer, Anne Uhlmann, Maria Valdés Hernández, Dick J. Veltman, Ganesan Venkatasubramanian, Nora C. Vetter, Daniella Vuletic, Susanne Walitza, Henrik Walter, Esther Walton, Zhen Wang, Joanna Wardlaw, Wei Wen, Lars T. WestlyeORCID, Barbara Franke, Paul M. Thompson, Simon E. Fisher, David C. Glahn, Bernard Mazoyer, Clyde Francks

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Abstract
The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders.