1. Developmental trajectories of neuroanatomical alterations associated with the 16p11.2 Copy Number Variations
- Author
-
Alonso, Cárdenas-de-la-Parra, Sandra, Martin-Brevet, Clara, Moreau, Borja, Rodriguez-Herreros, Vladimir, S Fonov, Anne, M Maillard, Nicole, R Zürcher, 2 European Consortium, 16p11., Nouchine Hadjikhani 48, Jacques, S Beckmann 49, Alexandre Reymond 50, Bogdan Draganski 51, Sébastien Jacquemont 52, D Louis Collins 1, Marie-Claude Addor, 7, Joris Andrieux, 8, Benoît Arveiler, 9, Geneviève Baujatm 10, Frédérique Sloan-Bénan 11, Marco, Belfiore, Dominique Bonneau 12, Sonia Bouquillon 13, Odile Boute 14, Brusco, Alfredo, Tiffany Busa 16, Jean-Hubert Caberg 17, Dominique Campion 18, Vanessa Colombert 19, Marie-Pierre Cordier 20, Albert David 21, François-Guillaume Debray 22, Marie-Ange Delrue 23, Martine Doco-Fenzy 24, Ulrike Dunkhase-Heinl 25, Patrick Edery 20, Christina Fagerberg 26, Laurence Faivre 27, Francesca, Forzano, David Genevieve 29, Marion Gérard 30, Giachino, Daniela Francesca, Agnès Guichet 32, Olivier Guillin 33, Delphine Héron 34, Bertrand Isidor 21, Aurélia Jacquette 34, Sylvie Jaillard 35, Hubert Journel 19, Boris Keren 36, Didier Lacombe, 9, Sébastien Lebon 37, Cédric Le Caignec 38, Marie-Pierre Lemaître 39, James Lespinasse 40, Michèle Mathieu-Dramart 41, Sandra Mercier 21, Cyril Mignot 34, Chantal Missirian 16, Florence Petit 42, Kristina Pilekær Sørensen 26, Lucile Pinson 29, Ghislaine Plessis 30, Fabienne Prieur 43, Caroline Rooryck-Thambo 44, Rossi, Massimiliano, Damien Sanlaville 45, Britta Schlott Kristiansen 26, Caroline Schluth-Bolard 45, Marianne Till 20, Mieke Van Haelst 46, Lionel Van Maldergem, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), McConnell Brain Imaging Centre (MNI), Montreal Neurological Institute and Hospital, McGill University = Université McGill [Montréal, Canada]-McGill University = Université McGill [Montréal, Canada], Ecophysiologie Végétale, Agronomie et Nutritions (EVA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Recherche Agronomique (INRA), Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS), Human Genetics, Université de Lausanne (UNIL), Service de génétique médicale, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, EHESP-Irset (EHESP-Irset), École des Hautes Études en Santé Publique [EHESP] (EHESP), CHU Pontchaillou [Rennes], National Institute of Child Health and Human Development, National Institute on Drug Abuse, 3388, MIRI Brain Canada, 201803PJT 400528 BSB, IVADO fund: a Canadian Institute of Health Research, Fonds de Recherche Nature et technologies du Québec, Roger De Spoelberch, Partridge Foundations, National Institute of Mental Health, N01-MH9-0002, National Institute of Neurological Disorders and Stroke, 33CS30-148401, National Science Foundation, MOP-111169, Canadian Institutes of Health Research, 31003A_160203, Schweizerischer Nationalfonds zur Fö, rderung der Wissenschaftlichen Forschung, Horizon 2020, Fondation Leenaards, and McGill University-McGill University
- Subjects
Adult ,Adolescent ,DNA Copy Number Variations ,Cognitive Neuroscience ,Biology ,computer.software_genre ,050105 experimental psychology ,Imaging ,White matter ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Neuroimaging ,Voxel ,Chromosome Duplication ,Gene duplication ,medicine ,Genetics ,Humans ,0501 psychology and cognitive sciences ,Copy-number variation ,Child ,ComputingMilieux_MISCELLANEOUS ,16p11.2 Copy number variants ,Brain development ,Neurodevelopmental disorders ,Normative growth trajectories ,[SCCO.NEUR]Cognitive science/Neuroscience ,05 social sciences ,Brain ,medicine.anatomical_structure ,Neurology ,Evolutionary biology ,Child, Preschool ,Endophenotype ,Human genome ,Chromosome Deletion ,Insula ,computer ,Chromosomes, Human, Pair 16 ,030217 neurology & neurosurgery - Abstract
Most of human genome is present in two copies (maternal and paternal). However, segments of the genome can be deleted or duplicated, and many of these genomic variations (known as Copy Number Variants) are associated with psychiatric disorders. 16p11.2 copy number variants (breakpoint 4–5) confer high risk for neurodevelopmental disorders and are associated with structural brain alterations of large effect-size. Methods used in previous studies were unable to investigate the onset of these alterations and whether they evolve with age. In this study, we aim at characterizing age-related effects of 16p11.2 copy number variants by analyzing a group with a broad age range including younger individuals. A large normative developmental dataset was used to accurately adjust for effects of age. We normalized volumes of segmented brain regions as well as volumes of each voxel defined by tensor-based morphometry. Results show that the total intracranial volumes, the global gray and white matter volumes are respectively higher and lower in deletion and duplication carriers compared to control subjects at 4.5 years of age. These differences remain stable through childhood, adolescence and adulthood until 23 years of age (range: 0.5 to 1.0 Z-score). Voxel-based results are consistent with previous findings in 16p11.2 copy number variant carriers, including increased volume in the calcarine cortex and insula in deletions, compared to controls, with an inverse effect in duplication carriers (1.0 Z-score). All large effect-size voxel-based differences are present at 4.5 years and seem to remain stable until the age of 23. Our results highlight the stability of a neuroimaging endophenotype over 2 decades during which neurodevelopmental symptoms evolve at a rapid pace.
- Published
- 2019
- Full Text
- View/download PDF