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      Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration

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      1 , * , , 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 5 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 18 , 19 , 20 , 21 , 22 , 23 , 5 , 24 , 25 , 26 , 16 , 10 , 11 , 22 , 27 , 22 , 10 , 11 , 3 , 4 , 28 , 12 , 13 , 14 , 29 , 27 , 3 , 30 , 31 , 6 , 12 , 32 , 20 , 1 , 1 , 1 , 1 , 33 , 34 , 35 , 36 , 37 , 38 , 24 , 24 , 39 , 34 , 34 , 22
      Frontiers in Psychiatry
      Frontiers Media S.A.
      Tourette syndrome, neuroimaging, genetics, ENIGMA, brain MRI

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          Abstract

          Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.

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          Most cited references100

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          Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

          Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association (GWA) meta-analysis based in 135,458 cases and 344,901 control, We identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression, and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relations of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine and define the basis of major depression and imply a continuous measure of risk underlies the clinical phenotype.
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            Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.
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              The Adolescent Brain Cognitive Development (ABCD) study: Imaging acquisition across 21 sites

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                Contributors
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                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                18 August 2022
                2022
                : 13
                : 958688
                Affiliations
                [1] 1Department of Biological Sciences, Purdue University , West Lafayette, IN, United States
                [2] 2Department of Psychiatry, Hannover University Medical School , Hannover, Germany
                [3] 3Max Planck Institute for Human Cognitive and Brain Sciences , Leipzig, Germany
                [4] 4Radiology Unit 1, Department of Medical Surgical Sciences and Advanced Technologies, University of Catania , Catania, Italy
                [5] 5University Medical Center Groningen, Department of Psychiatry, University of Groningen , Groningen, Netherlands
                [6] 6Department of Child and Adolescent Psychiatry, Technische Universität (TU) Dresden , Dresden, Germany
                [7] 7Department of Pediatrics, Herlev University Hospital , Herlev, Denmark
                [8] 8Department of Neurophysiology, Pitié-Salpêtrière Hospital, Sorbonne University , Paris, France
                [9] 9Pitié-Salpêtrière Hospital , Paris, France
                [10] 10Unidad de Trastornos del Movimiento, Servicio de Neurología y Neurofisiología Clínica, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/University of Seville , Seville, Spain
                [11] 11Centro de Investigación Biomédica en Red Sobre Enfermedades Neurodegenerativas (CIBERNED), Instituto de Salud Carlos III , Madrid, Spain
                [12] 12Department of Psychiatry, Psychotherapy and Psychosomatic, RWTH Aachen University , Aachen, Germany
                [13] 13Institute of Neuroscience and Medicine 4, Forschungszentrum Jülich GmbH , Jülich, Germany
                [14] 14JARA BRAIN—Translational Medicine , Aachen, Germany
                [15] 15Department of Biological and Medical Psychology, University of Bergen , Bergen, Norway
                [16] 16Shanghai Research Center for Brain Science and Brain-Inspired Intelligence , Shanghai, China
                [17] 17Department of Psychiatry, Medical University of Warsaw , Warsaw, Poland
                [18] 18Institute of Systems Motor Science, University of Lübeck , Lübeck, Germany
                [19] 19Department of Psychiatry and Psychotherapy, Ludwig Maximilians University of Munich , Munich, Germany
                [20] 20Deakin University , Geelong, VIC, Australia
                [21] 21Wake Forest School of Medicine , Winston-Salem, NC, United States
                [22] 22Department of Psychiatry, Washington University in St. Louis , St. Louis, MO, United States
                [23] 23Centre for Innovation in Mental Health, School of Psychology, University of Southampton , Southampton, United Kingdom
                [24] 24Radboud University Medical Centre, Donders Institute for Brain, Cognition and Behaviour , Nijmegen, Netherlands
                [25] 25Department of Neurology, Charité-University Medicine Berlin , Berlin, Germany
                [26] 26Department of Cognitive Science, University of California, San Diego , La Jolla, CA, United States
                [27] 27Department of Neurology, Medical University of Warsaw , Warsaw, Poland
                [28] 28Child and Adolescent Neurology and Psychiatric Section, Department of Clinical and Experimental Medicine, Catania University , Catania, Italy
                [29] 29Child Neuropsychiatry Unit, Department of Clinical and Experimental Medicine, School of Medicine, University of Catania , Catania, Italy
                [30] 30Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen, Denmark
                [31] 31Department of Clinical Genetics, Kennedy Center, Copenhagen University Hospital Rigshospitalet , Glostrup, Denmark
                [32] 32Department of Child Psychiatry, Medical University of Warsaw , Warsaw, Poland
                [33] 33Department of Computer Science, Purdue University , West Lafayette, IN, United States
                [34] 34Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California , Los Angeles, CA, United States
                [35] 35Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC–Sophia Children’s Hospital, University Medical Center Rotterdam , Rotterdam, Netherlands
                [36] 36Department of Psychiatry, Amsterdam Neuroscience, Amsterdam UMC , Amsterdam, Netherlands
                [37] 37Centre for Youth Mental Health, University of Melbourne , Melbourne, VIC, Australia
                [38] 38South African Medical Research Council (SAMRC) Unit on Risk and Resilience in Mental Disorders, Department of Psychiatry and Neuroscience Institute, University of Cape Town , Cape Town, South Africa
                [39] 39Department Psychiatry, Department Anatomy and Neuroscience, Amsterdam University Medical Center (UMC), Vrije Universiteit Amsterdam, Amsterdam Neuroscience , Amsterdam, Netherlands
                Author notes

                Edited by: Roberto Canitano, Siena University Hospital, Italy

                Reviewed by: Michael H. Bloch, Yale University, United States; A. Cavanna, Birmingham and Solihull Mental Health NHS Foundation Trust, United Kingdom

                *Correspondence: Peristera Paschou, ppaschou@ 123456purdue.edu

                This article was submitted to Neuroimaging and Stimulation, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2022.958688
                9443935
                36072455
                dc3c0195-ffea-4d7e-ab91-e8d86d43a056
                Copyright © 2022 Paschou, Jin, Müller-Vahl, Möller, Rizzo, Hoekstra, Roessner, Mol Debes, Worbe, Hartmann, Mir, Cath, Neuner, Eichele, Zhang, Lewandowska, Munchau, Verrel, Musil, Silk, Hanlon, Bihun, Brandt, Dietrich, Forde, Ganos, Greene, Chu, Grothe, Hershey, Janik, Koller, Martin-Rodriguez, Müller, Palmucci, Prato, Ramkiran, Saia, Szejko, Torrecuso, Tumer, Uhlmann, Veselinovic, Wolańczyk, Zouki, Jain, Topaloudi, Kaka, Yang, Drineas, Thomopoulos, White, Veltman, Schmaal, Stein, Buitelaar, Franke, van den Heuvel, Jahanshad, Thompson and Black.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 31 May 2022
                : 18 July 2022
                Page count
                Figures: 2, Tables: 0, Equations: 0, References: 100, Pages: 11, Words: 8115
                Categories
                Psychiatry
                Perspective

                Clinical Psychology & Psychiatry
                tourette syndrome,neuroimaging,genetics,enigma,brain mri
                Clinical Psychology & Psychiatry
                tourette syndrome, neuroimaging, genetics, enigma, brain mri

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