Title: | 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans. |
Authors: | Sønderby, Ida E van der Meer, Dennis Moreau, Clara Kaufmann, Tobias Walters, G Bragi Ellegaard, Maria Abdellaoui, Abdel Ames, David Amunts, Katrin Andersson, Micael Armstrong, Nicola J Bernard, Manon Blackburn, Nicholas B Blangero, John Boomsma, Dorret I Brodaty, Henry Brouwer, Rachel M Bülow, Robin Bøen, Rune Cahn, Wiepke Calhoun, Vince D Caspers, Svenja Ching, Christopher R K Cichon, Sven Ciufolini, Simone Crespo-Facorro, Benedicto Curran, Joanne E Dale, Anders M Dalvie, Shareefa Dazzan, Paola de Geus, Eco J C de Zubicaray, Greig I de Zwarte, Sonja M C Desrivieres, Sylvane Doherty, Joanne L Donohoe, Gary Draganski, Bogdan Ehrlich, Stefan Eising, Else Espeseth, Thomas Fejgin, Kim Fisher, Simon E Fladby, Tormod Frei, Oleksandr Frouin, Vincent Fukunaga, Masaki Gareau, Thomas Ge, Tian Glahn, David C Grabe, Hans J Groenewold, Nynke A Gústafsson, Ómar Haavik, Jan Haberg, Asta K Hall, Jeremy Hashimoto, Ryota Hehir-Kwa, Jayne Y Hibar, Derrek P Hillegers, Manon H J Hoffmann, Per Holleran, Laurena Holmes, Avram J Homuth, Georg Hottenga, Jouke-Jan Hulshoff Pol, Hilleke E Ikeda, Masashi Jahanshad, Neda Jockwitz, Christiane Johansson, Stefan Jönsson, Erik G Jørgensen, Niklas R Kikuchi, Masataka Knowles, Emma E M Kumar, Kuldeep Le Hellard, Stephanie Leu, Costin Linden, David E J Liu, Jingyu Lundervold, Arvid Lundervold, Astri Johansen Maillard, Anne M Martin, Nicholas G Martin-Brevet, Sandra Mather, Karen A Mathias, Samuel R McMahon, Katie L McRae, Allan F Medland, Sarah E Meyer-Lindenberg, Andreas Moberget, Torgeir Modenato, Claudia Sánchez, Jennifer Monereo Morris, Derek W Mühleisen, Thomas W Murray, Robin M Nielsen, Jacob Nordvik, Jan E Nyberg, Lars Loohuis, Loes M Olde Ophoff, Roel A Owen, Michael J Paus, Tomas Pausova, Zdenka Peralta, Juan M Pike, G Bruce Prieto, Carlos Quinlan, Erin B Reinbold, Céline S Marques, Tiago Reis Rucker, James J H Sachdev, Perminder S Sando, Sigrid B Schofield, Peter R Schork, Andrew J Schumann, Gunter Shin, Jean Shumskaya, Elena Silva, Ana I Sisodiya, Sanjay M Steen, Vidar M Stein, Dan J Strike, Lachlan T Suzuki, Ikuo K Tamnes, Christian K Teumer, Alexander Thalamuthu, Anbupalam Tordesillas-Gutiérrez, Diana Uhlmann, Anne Ulfarsson, Magnus O van 't Ent, Dennis van den Bree, Marianne B M Vanderhaeghen, Pierre Vassos, Evangelos Wen, Wei Wittfeld, Katharina Wright, Margaret J Agartz, Ingrid Djurovic, Srdjan Westlye, Lars T Stefansson, Hreinn Stefansson, Kari Jacquemont, Sébastien Thompson, Paul M Andreassen, Ole A ENIGMA-CNV working group |
metadata.dc.subject.mesh: | Brain Chromosome Deletion Cognition DNA Copy Number Variations Female Humans Male Schizophrenia |
Issue Date: | 22-Mar-2021 |
Abstract: | Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function. |
URI: | http://hdl.handle.net/10668/17384 |
metadata.dc.identifier.doi: | 10.1038/s41398-021-01213-0 |
Appears in Collections: | Producción 2020
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