Article (Scientific journals)
Effects of eight neuropsychiatric copy number variants on human brain structure
Modenato, C.; Kumar, K.; Moreau, C. et al.
2021In Translational Psychiatry, 11 (1)
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Abstract :
[en] 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).
Disciplines :
Genetics & genetic processes
Author, co-author :
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, C.-O.;  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, A.-R.;  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, A.M.;  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
Addor, M.-C.;  Service de génétique médicale, Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland
Andrieux, J.;  Institut de Génétique Médicale, CHRU de Lille, Hopital Jeanne de Flandre, Lille, France
Arveiler, B.;  Service de génétique médicale, CHU de Bordeaux- GH Pellegrin, Bordeaux, France
Baujat, G.;  Service de Génétique Médicale, CHU Paris - Hôpital Necker-Enfants Malades, Paris, France
Sloan-Béna, F.;  Service de médecine génétique, Hôpitaux Universitaires de Genève – HUG, Geneva, Switzerland
Belfiore, M.;  Service de génétique médicale, Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland
Bonneau, D.;  Service de génétique médicale, CHU d’Angers, Angers, France
Bouquillon, S.;  Institut de Génétique Médicale, Hopital Jeanne de Flandre, Lille, France
Boute, O.;  Hôpital Jeanne de Flandre, CHRU de Lille, Lille, France
Brusco, A.;  Genetica Medica, Dipartimento di Scienze Mediche, Università di Torino, Torino, Italy
Busa, T.;  Département de génétique médicale, CHU de Marseille, Hôpital de la Timone, Marseille, France
CABERG, Jean-Hubert ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Campion, D.;  Service de psychiatrie, Centre hospitalier de Rouvray, Sotteville lès Rouen, France
Colombert, V.;  Service de génétique médicale, Centre Hospitalier Bretagne Atlantique CH Chubert, Vannes, France
Cordier, M.-P.;  Service de génétique clinique, CHU de Lyon, Hospices Civils de Lyon, Lyon, France
David, A.;  Service de Génétique Médicale, CHU de Nantes, Hôtel Dieu, Paris, France
Debray, François-Guillaume ;  Centre Hospitalier Universitaire de Liège - CHU > > Service de génétique
Delrue, M.-A.;  Service de génétique médicale, CHU de Bordeaux, Hôpital Pellegrin, Bordeaux, France
Doco-Fenzy, M.;  Service de Génétique et Biologie de la Reproduction, CHU de Reims, Hôpital Maison Blanche, Reims, France
Dunkhase-Heinl, U.;  Department of Pediatrics, Aabenraa Hospital, Sonderjylland, Denmark
Edery, P.;  Service de génétique clinique, CHU de Lyon, Hospices Civils de Lyon, Lyon, France
Fagerberg, C.;  Department of Clinical Genetics, Odense University hospital, Odense, Denmark
Faivre, L.;  Centre de génétique, Hôpital d’Enfants, CHU Dijon Bourgogne - Hôpital François Mitterrand, Dijon, France
Forzano, F.;  Ambulatorio di Genetica Medica, Ospedali Galliera di Genova, Genoa, Italy, Clinical Genetics Department, 7th Floor Borough Wing, Guy’s Hospital, Guy’s & St Thomas’ NHS Foundation Trust, Great Maze Pond, London, SE1 9RT, United Kingdom
Genevieve, D.;  Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, service de génétique clinique, Université Montpellier, Unité Inserm U1183, CHU Montpellier, Montpellier, France
Gérard, M.;  Service de Génétique, CHU de Caen, Hôpital Clémenceau, Caen, France
Giachino, D.;  Genetica Medica, Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Torino, Italy
Guichet, A.;  Service de génétique, CHU d’Angers, Angers, France
Guillin, O.;  Service de psychiatrie, Centre hospitalier du Rouvray, Sotteville lès Rouen, France
Héron, D.;  Service de Génétique clinique, CHU Paris-GH La Pitié Salpêtrière-Charles Foix - Hôpital Pitié Salpêtrière, Paris, France
Isidor, B.;  Service de Génétique Médicale, CHU de Nantes, Hôtel Dieu, Paris, France
Jacquette, A.;  Service de Génétique clinique, CHU Paris-GH La Pitié Salpêtrière-Charles Foix - Hôpital Pitié-Salpêtrière, Foix, France
Jaillard, S.;  Service de Génétique Moléculaire et Génomique – Pôle biologie, CHU de Rennes, Hôpital Pontchaillou, Rennes, France
Journel, H.;  Service de génétique médicale, Centre Hospitalier Bretagne Atlantique CH Chubert, Vannes, France
Keren, B.;  Centre de Génétique Moléculaire et Chromosomique, CHU Paris-GH La Pitié Salpêtrière-Charles Foix - Hôpital Pitié-Salpêtrière, Paris, France
Lacombe, D.;  Service de génétique médicale, CHU de Bordeaux-GH Pellegrin, Bordeaux, France
Lebon, S.;  Pediatric Neurology Unit, Department of Pediatrics, Lausanne University Hospital, Lausanne, Switzerland
Le Caignec, C.;  Service de Génétique Médicale - Institut de Biologie, CHU de Nantes, Nantes, France
Lemaître, M.-P.;  Service de Neuropédiatrie, Centre Hospitalier Régional Universitaire de Lille, Lille, France
Lespinasse, J.;  Service génétique médicale et oncogénétique, Hotel Dieu, Chambéry, France
Mathieu-Dramart, M.;  Service de Génétique Clinique, CHU Amiens Picardie, Amiens, France
Mercier, S.;  Service de Génétique Médicale, CHU de Nantes, Hôtel Dieu, Paris, France
Mignot, C.;  Service de Génétique clinique, CHU Paris-GH La Pitié Salpêtrière-Charles Foix - Hôpital Pitié-Salpêtrière, Paris, France
Missirian, C.;  Département de génétique médicale, CHU de Marseille, Hôpital de la Timone, Marseille, France
Petit, F.;  Service de génétique clinique Guy Fontaine, Hôpital Jeanne de Flandre, CHRU de Lille, Lille, France
Pilekær Sørensen, K.;  Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
Pinson, L.;  Département de Génétique Médicale, Maladies Rares et Médecine Personnalisée, service de génétique clinique, Université Montpellier, Unité Inserm U1183, CHU Montpellier, Montpellier, France
Plessis, G.;  Service de Génétique, CHU de Caen, Hôpital Clémenceau, Caen, France
Prieur, F.;  Service de génétique clinique, CHU de Saint-Etienne - Hôpital Nord, Saint-Priest-en-Jarez, France
Raymond, A.;  Center for Integrative Genomics, Lausanne University, Lausanne, Switzerland
Rooryck-Thambo, C.;  Laboratoire de génétique moléculaire, CHU de Bordeaux-GH Pellegrin, Bordeaux, France
Rossi, M.;  Service de génétique clinique, CHU de Lyon, Hospices Civils de Lyon, Lyon, France
Sanlaville, D.;  Laboratoire de Cytogénétique Constitutionnelle, CHU de Lyon, Hospices Civils de Lyon, Lyon, France
Schlott Kristiansen, B.;  Department of Clinical Genetics, Odense University Hospital, Odense, Denmark
Schluth-Bolard, C.;  Laboratoire de Cytogénétique Constitutionnelle, CHU de Lyon, Hospices Civils de Lyon, Lyon, France
Till, M.;  Service de génétique clinique, CHU de Lyon, Hospices Civils de Lyon, Lyon, France
Van Haelst, M.;  Department of Genetics, University Medical Center Utrecht, Utrecht, Netherlands
Van Maldergem, L.;  Centre de Génétique humaine, CHRU de Besançon - Hôpital Saint-Jacques, Besançon, France
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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, United States
Silva, A.I.;  School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom
van den Bree, M.B.M.;  MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom
Linden, D.E.J.;  School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom
Owen, M.J.;  MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom
Hall, J.;  MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom, Division of Psychological Medicine and Clinical Neurosciences, School of Medicine, Cardiff University, Cardiff, United Kingdom, Neuroscience and Mental Health Research Institute, Cardiff University, Cardiff, United Kingdom
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, C.E.;  Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles, United States
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
16p11.2 European Consortium
Simons Searchlight Consortium
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Language :
English
Title :
Effects of eight neuropsychiatric copy number variants on human brain structure
Publication date :
2021
Journal title :
Translational Psychiatry
eISSN :
2158-3188
Publisher :
Springer Nature
Volume :
11
Issue :
1
Peer reviewed :
Peer Reviewed verified by ORBi
Funding text :
This research was supported by Calcul Quebec (http://www.calculquebec.ca) and Compute Canada (http://www.computecanada.ca), the Brain Canada Multi-Investigator initiative, the Canadian Institutes of Health Research, CIHR_400528, The Institute of Data Valorization (IVADO) through the Canada First Research
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