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Dose response of the 16p11.2 distal copy number variant on intracranial volume and basal ganglia

2018; Springer Nature; Volume: 25; Issue: 3 Linguagem: Inglês

10.1038/s41380-018-0118-1

1476-5578

Ida E. Sønderby, Ómar Gústafsson, Nhat Trung Doan, Derrek P. Hibar, Sandra Martin‐Brevet, Abdel Abdellaoui, David Ames, Katrin Amunts, Michael Andersson, Nicola J. Armstrong, Manon Bernard, Nicholas B. Blackburn, John Blangero, Dorret I. Boomsma, Janita Bralten, Hans-Richard Brattbak, Henry Brodaty, Rachel M. Brouwer, Robin Bülow, Vince D. Calhoun, Svenja Caspers, Gianpiero L. Cavalleri, Chi‐Hua Chen, Sven Cichon, Simone Ciufolini, Aiden Corvin, Benedicto Crespo‐Facorro, Joanne E. Curran, Anders M. Dale, Shareefa Dalvie, Paola Dazzan, Eco J. C. de Geus, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Norman Delanty, Anouk den Braber, Sylvane Desrivières, Gary Donohoe, Bogdan Draganski, Stefan Ehrlich, Thomas Espeseth, Simon E. Fisher, Barbara Franke, Vincent Frouin, Masaki Fukunaga, Thomas Gareau, David C. Glahn, Hans J. Grabe, Nynke A. Groenewold, Jan Haavik, Asta K. Håberg, Ryota Hashimoto, Jayne Y. Hehir‐Kwa, Andreas Heinz, Manon H. J. Hillegers, Per Hoffmann, Laurena Holleran, Jouke‐Jan Hottenga, Hilleke E Hulshoff, Masashi Ikeda, Neda Jahanshad, Terry L. Jernigan, Christiane Jockwitz, Stefan Johansson, Guðrún A. Jónsdóttir, Erik G. Jönsson, René S. Kahn, Tobias Kaufmann, Sinéad Kelly, Masataka Kikuchi, Emma E. M. Knowles, Knut K. Kolskår, John B. Kwok, Stéphanie Le Hellard, Costin Leu, Jingyu Liu, Astri J. Lundervold, Arvid Lundervold, Nicholas G. Martin, Karen A. Mather, Samuel R. Mathias, Mark McCormack, Katie L. McMahon, Allan F. McRae, Yuri Milaneschi, Clara Moreau, Derek W. Morris, David Mothersill, Thomas W. Mühleisen, Robin M. Murray, Jan Egil Nordvik, Lars Nyberg, Loes M. Olde Loohuis, Roel A. Ophoff, Tomáš Paus, Zdenka Pausová, Brenda W.J.H. Penninx, Juan M. Peralta, G. Bruce Pike, Carlos Alberto Vanegas Prieto, Sara Pudas, Erin Burke Quinlan, Daniel Quintana, Céline S. Reinbold, Tiago Reis Marques, Alexandre Reymond, Geneviève Richard, Borja Rodríguez‐Herreros, Roberto Roiz‐Santiáñez, Jarek Rokicki, James Rucker, Perminder S. Sachdev, Anne‐Marthe Sanders, Sigrid Botne Sando, Lianne Schmaal, Peter R. Schofield, Andrew J. Schork, Günter Schumann, Jean Shin, Elena Shumskaya, Sanjay M. Sisodiya, Vidar M. Steen, Dan J. Stein, Stacy Steinberg, Lachlan T. Strike, Alexander Teumer, Anbupalam Thalamuthu, Diana Tordesillas‐Gutiérrez, Jessica A. Turner, Torill Ueland, Anne Uhlmann, Magnús Ö. Úlfarsson, Dennis van ‘t Ent, Dennis van der Meer, Neeltje E. M. van Haren, Anja Vaskinn, Evangelos Vassos, G. Bragi Walters, Yunpeng Wang, Wei Wen, Christopher D. Whelan, Katharina Wittfeld, Margaret J. Wright, Hidenaga Yamamori, Tetyana Zayats, Ingrid Agartz, Lars T. Westlye, Sébastien Jacquemont, Srdjan Djurovic, Hreinn Stefánsson, Kāri Stefánsson, Paul M. Thompson, Ole A. Andreassen,

Genomics and Rare Diseases

Carriers of large recurrent copy number variants (CNVs) have a higher risk of developing neurodevelopmental disorders. The 16p11.2 distal CNV predisposes carriers to e.g., autism spectrum disorder and schizophrenia. We compared subcortical brain volumes of 12 16p11.2 distal deletion and 12 duplication carriers to 6882 non-carriers from the large-scale brain Magnetic Resonance Imaging collaboration, ENIGMA-CNV. After stringent CNV calling procedures, and standardized FreeSurfer image analysis, we found negative dose-response associations with copy number on intracranial volume and on regional caudate, pallidum and putamen volumes (β = -0.71 to -1.37; P < 0.0005). In an independent sample, consistent results were obtained, with significant effects in the pallidum (β = -0.95, P = 0.0042). The two data sets combined showed significant negative dose-response for the accumbens, caudate, pallidum, putamen and ICV (P = 0.0032, 8.9 × 10