Effects of eight neuropsychiatric copy number variants on human brain structure.

Autor:	Modenato C; LREN - Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland., Kumar K; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Moreau C; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Martin-Brevet S; LREN - Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland., Huguet G; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Schramm C; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Jean-Louis M; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Martin CO; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Younis N; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Tamer P; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Douard E; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Thébault-Dagher F; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Côté V; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Charlebois AR; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Deguire F; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Maillard AM; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland., Rodriguez-Herreros B; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland., Pain A; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland., Richetin S; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland., Melie-Garcia L; Applied Signal Processing Group (ASPG), Swiss Federal Institute Lausanne (EPFL), Lausanne, Switzerland., Kushan L; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles, USA., Silva AI; School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK., van den Bree MBM; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.; Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.; Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK., Linden DEJ; School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands.; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.; Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK., Owen MJ; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.; Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK., Hall J; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.; Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, UK.; Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, UK., Lippé S; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada., Chakravarty M; Douglas Research Centre, McGill University, Montréal, QC, Canada., Bzdok D; Department of Biomedical Engineering, McConnell Brain Imaging Centre; Montreal Neurological Institute, McGill University, Montréal, QC, Canada.; Mila - Quebec Artificial Intelligence Institute, Montréal, QC, Canada., Bearden CE; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles, USA., Draganski B; LREN - Department of Clinical Neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland.; Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany., Jacquemont S; Centre de recherche CHU Sainte-Justine and University of Montréal, Montréal, Canada. sebastien.jacquemont@umontreal.ca.
Jazyk:	angličtina
Zdroj:	Translational psychiatry [Transl Psychiatry] 2021 Jul 20; Vol. 11 (1), pp. 399. Date of Electronic Publication: 2021 Jul 20.
DOI:	10.1038/s41398-021-01490-9
Abstrakt:	Many copy number variants (CNVs) confer risk for the same range of neurodevelopmental symptoms and psychiatric conditions including autism and schizophrenia. Yet, to date neuroimaging studies have typically been carried out one mutation at a time, showing that CNVs have large effects on brain anatomy. Here, we aimed to characterize and quantify the distinct brain morphometry effects and latent dimensions across 8 neuropsychiatric CNVs. We analyzed T1-weighted MRI data from clinically and non-clinically ascertained CNV carriers (deletion/duplication) at the 1q21.1 (n = 39/28), 16p11.2 (n = 87/78), 22q11.2 (n = 75/30), and 15q11.2 (n = 72/76) loci as well as 1296 non-carriers (controls). Case-control contrasts of all examined genomic loci demonstrated effects on brain anatomy, with deletions and duplications showing mirror effects at the global and regional levels. Although CNVs mainly showed distinct brain patterns, principal component analysis (PCA) loaded subsets of CNVs on two latent brain dimensions, which explained 32 and 29% of the variance of the 8 Cohen's d maps. The cingulate gyrus, insula, supplementary motor cortex, and cerebellum were identified by PCA and multi-view pattern learning as top regions contributing to latent dimension shared across subsets of CNVs. The large proportion of distinct CNV effects on brain morphology may explain the small neuroimaging effect sizes reported in polygenic psychiatric conditions. Nevertheless, latent gene brain morphology dimensions will help subgroup the rapidly expanding landscape of neuropsychiatric variants and dissect the heterogeneity of idiopathic conditions. (© 2021. The Author(s).)
Databáze:	MEDLINE
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