Subcortical brain alterations in carriers of genomic copy number variants.

Autor:	Kumar K; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Modenato C; LREN - Department of clinical neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland., Moreau C; Institut Pasteur, Université de Paris, CNRS UMR 3571, Human Genetics and Cognitive Functions, 25 rue du Dr. Roux, Paris, France., Ching CRK; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA., Harvey A; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Martin-Brevet S; LREN - Department of clinical neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland., Huguet G; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Jean-Louis M; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Douard E; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Martin CO; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Younis N; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Tamer P; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Maillard AM; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland., Rodriguez-Herreros B; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland., Pain A; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland., Richetin S; Service des Troubles du Spectre de l'Autisme et apparentés, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland., Kushan L; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles, USA., Isaev D; Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA., Alpert K; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA., Ragothaman A; Department of biomedical engineering, Oregon Health and Science university, Portland, Oregon, USA., Turner JA; Psychology & Neuroscience, Georgia State University, Atlanta, Georgia, USA., Wang L; Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.; Department of Psychiatry and Behavioral Health, Ohio State University Wexner Medical Center, Columbus, Ohio, USA., Ho TC; Department of Psychiatry & Behavioral Sciences, Stanford University, Stanford, CA, USA.; Department of Psychology, Stanford University, Stanford, CA USA., Schmaal L; Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, Australia.; Centre for Youth Mental Health, The University of Melbourne, Melbourne, Australia., Silva AI; School for Mental Health and Neuroscience, Maastricht University, Netherlands.; MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, United Kingdom., van den Bree MBM; 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 DEJ; School for Mental Health and Neuroscience, Maastricht University, 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 MJ; 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, Canada., Dumas G; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada., Draganski B; LREN - Department of clinical neurosciences, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Switzerland.; Neurology Department, Max-Planck-Institute for Human Cognitive and Brain Sciences, Leipzig, Germany., Gutman BA; Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, Illinois, USA., Sønderby IE; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and University of Oslo, Oslo, Norway.; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway.; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway., Andreassen OA; NORMENT, Division of Mental Health and Addiction, Oslo University Hospital and University of Oslo, Oslo, Norway.; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway., Schultz L; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, PA, USA.; Lifespan Brain Institute of Children's Hospital of Philadelphia and Penn Medicine, PA, USA., Almasy L; Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, PA, USA.; Lifespan Brain Institute of Children's Hospital of Philadelphia and Penn Medicine, PA, USA.; Department of Genetics, University of Pennsylvania, PA, USA., Glahn DC; Harvard Medical School, Department of Psychiatry, 25 Shattuck St, Boston, MA 02115, USA.; Boston Children's Hospital, Tommy Fuss Center for Neuropsychiatric Disease Research, 300 Longwood Avenue, Boston, MA 02115, USA., Bearden CE; Semel Institute for Neuroscience and Human Behavior, Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles, USA., Thompson PM; Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, California, USA., Jacquemont S; Centre de recherche CHU Sainte-Justine and University of Montréal, Canada.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2023 Feb 22. Date of Electronic Publication: 2023 Feb 22.
DOI:	10.1101/2023.02.14.23285913
Abstrakt:	Objectives: Copy number variants (CNVs) are well-known genetic pleiotropic risk factors for multiple neurodevelopmental and psychiatric disorders (NPDs) including autism (ASD) and schizophrenia (SZ). Overall, little is known about how different CNVs conferring risk for the same condition may affect subcortical brain structures and how these alterations relate to the level of disease risk conferred by CNVs. To fill this gap, we investigated gross volume, and vertex level thickness and surface maps of subcortical structures in 11 different CNVs and 6 different NPDs. Methods: Subcortical structures were characterized using harmonized ENIGMA protocols in 675 CNV carriers (at the following loci: 1q21.1, TAR, 13q12.12, 15q11.2, 16p11.2, 16p13.11, and 22q11.2) and 782 controls (Male/Female: 727/730; age-range: 6-80 years) as well as ENIGMA summary-statistics for ASD, SZ, ADHD, Obsessive-Compulsive-Disorder, Bipolar-Disorder, and Major-Depression. Results: Nine of the 11 CNVs affected volume of at least one subcortical structure. The hippocampus and amygdala were affected by five CNVs. Effect sizes of CNVs on subcortical volume, thickness and local surface area were correlated with their previously reported effect sizes on cognition and risk for ASD and SZ. Shape analyses were able to identify subregional alterations that were averaged out in volume analyses. We identified a common latent dimension - characterized by opposing effects on basal ganglia and limbic structures - across CNVs and across NPDs. Conclusion: Our findings demonstrate that subcortical alterations associated with CNVs show varying levels of similarities with those associated with neuropsychiatric conditions. We also observed distinct effects with some CNVs clustering with adult conditions while others clustered with ASD. This large cross-CNV and NPDs analysis provide insight into the long-standing questions of why CNVs at different genomic loci increase the risk for the same NPD, as well as why a single CNV increases the risk for a diverse set of NPDs.
Databáze:	MEDLINE
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