Accès ouvert déclaré 2025 preprint

A cross-disorder analysis of CNVs finds novel loci and dose-dependent relationships of genes to psychiatric traits

Omar Shanta, Marieke Klein, M Sacks, Jeffrey R. MacDonald, Adam X. Maihofer, Mohammad Ahangari, Worrawat Engchuan, Bhooma Thiruvahindrapuram, James P. Guevara, Oanh Hong, Guillaume Huguet, Ida E. Sønderby, Maria Kalyuzhny, Mark J. Adams, Rolf Adolfsson, Ingrid Agartz, Allison E. Aiello, Martin Alda, Judith Allardyce, Ananda B. Amstadter, Till F. M. Andlauer, Ole A. Andreassen, María S. Artigas, S. Bryn Austin, Muhammad Ayub, Dewleen G. Baker, Bernhard T. Baune, Joanna M. Biernacka, Tim B. Bigdeli, Jonathan I. Bisson, D. Blackwood, Marco P. Boks, David Braff, Elvira Bramon, Gerome Breen, T. Brueckl, Richard A. Bryant, Cynthia M. Bulik, Joseph D. Buxbaum, Murray J. Cairns, José Miguel Caldas‐de‐Almeida, Megan Campbell, Dominique Campion, Vaughan J. Carr, Enrique Castelao, Boris Chaumette, Sven Cichon, David Cohen, Aiden Corvin, Jennifer Crosbie, Udo Dannlowski, Franziska Degenhardt, Douglas L. Delahanty, Astrid Dempfle, Guillaume Desachy, Arianna Di Florio, Faith Dickerson, Srdjan Djurovic, Katharina Domschke, Lisa Douglas, Ole Kristian Drange, Laramie E. Duncan, Howard J. Edenberg, Tõnu Esko, Stephen V. Faraone, Norah C. Feeny, Andreas J. Forstner, Barbara Franke, Mark A. Frye, Dong‐Jing Fu, Janice M. Fullerton, А. Э. Гареева, Linda Garvert, Justine M. Gatt, Pablo V. Gejman, Daniel H. Geschwind, Ina Giegling, Stephen J. Glatt, Fernando S. Goes, Katherine Gordon‐Smith, Hans J. Grabe, Melissa J. Green, Michael F. Green, Tiffany A. Greenwood, Maria Grigoroiu‐Serbânescu, Raquel E. Gur, Ruben C. Gur, José Guzmán‐Parra, Jan Haavik, Tim Hahn, Håkon Håkonarson, Joachim Hallmayer, Marian L. Hamshere, Annette M. Hartmann, Arsalan Hassan, Caroline Hayward, Johannes Hebebrand, Sian Hemmings, Stefan Herms, Marisol Herrera-Rivero, Anke Hinney, Georg Homuth, Andrés Ingason, Lucas Toshio Ito, Ian Jones, Lisa Jones, Lina Jönsson, Erik G. Jönsson, René S. Kahn, Robert Karlsson, Milissa L. Kaufman, John R. Kelsoe, James L. Kennedy, Anthony P. King, Tilo Kircher, George Kirov, Per M. Knappskog, James A. Knowles, Karestan C. Koenen, Bettina Konte, Mayuresh S. Korgaonkar, Kaarina Kowalec, Marie‐Odile Krebs, Mikael Landén, Claudine Laurent‐Levinson, Lauren A. M. Lebois, Doug Levinson, Cathryn M. Lewis, Qingqin S. Li, Israel Liberzon, Greg Light, Sandra K. Loo, Yi Lu, Susanne Lucae, Charles R. Marmar, Nick Martin, Fermín Mayoral, Andrew M. McIntosh, Katie A. McLaughlin, Samuel A. McLean, Andrew McQuillin, Sarah E. Medland, Andreas Meyer‐Lindenberg, Vihra Milanova, Philip B. Mitchell, Esther Molina, Bryan Mowry, Bertram Müller‐Myhsok, Niamh Mullins, Robin Murray, Markus M. Nöthen, John I. Nürnberger, Kevin S. O’Connell, Roel A. Ophoff, Holly K. Orcutt, Michael J. Owen, Aarno Palotie, Carlos N. Pato, Michele T. Pato, Joanna Pawlak, Triinu Peters, Tracey L. Petryshen, Giorgio Pistis, James B. Potash, John Powell, Martin Preisig, Digby Quested, Josep Antoni Ramos‐Quiroga, Andreas Reif, Kerry J. Ressler, Marta Ribasés, Marcella Rietschel, Victoria B. Risbrough, Margarita Rivera, Alex O. Rothbaum, Barbara O. Rothbaum, Dan Rujescu, Takeo Saito, Alan R. Sanders, Russell Schachar, Peter R. Schofield, Eva C. Schulte, Thomas G. Schulze, Laura J. Scott, Soraya Seedat, Christina M. Sheerin, Jianxin Shi, Pamela Sklar, Susan L. Smalley, Olav B. Smeland, Jordan W. Smoller, Edmund Sonuga‐Barke, David St Clair, Nils Eiel Steen, Dan J. Stein, Frederike Stein, Murray B. Stein, Fabian Streit, Neal R. Swerdlow, Florence Thibaut, Johan H. Thygesen, И. Ф. Тимербулатов, Claudio Toma, Edward Trapido, Micheline Tremblay, Ming T. Tsuang, Monica Uddin, Marquis P. Vawter, John B. Vincent, Henry Völzke, James Walters, Cynthia Shannon Weickert, Lauren A. Weiss, Myrna M. Weissman, Thomas Werge, Stephanie H. Witt, Miguel Xavier, Robert H. Yolken, Ross McD. Young, Tetyana Zayats, Lori A. Zoellner, Kimberley Kendall, Brien P. Riley, Naomi R. Wray, Michael O‘Donovan, Patrick F. Sullivan, Sandra Sanchez‐Roige, Caroline M. Nievergelt, Sébastien Jacquemont, Stephen W. Scherer, Jonathan Sebat

6Citations signalées — pas une note de qualité

186Institutions déclarées

28Pays d’affiliation déclarés

Résumé fourni par la source

Abstract Rare copy number variants (CNVs) are a key component of the genetic basis of psychiatric conditions, but have not been well characterized for most. We conducted a genome-wide CNV analysis across six diagnostic categories (N = 574,965): autism (ASD), ADHD, bipolar disorder (BD), major depressive disorder (MDD), PTSD, and schizophrenia (SCZ). We identified 35 genome-wide significant associations at 18 loci, including novel associations in SCZ ( SMYD3, USP7 - HAPSTR1 ) and in the combined cross-disorder analysis ( ASTN2 ). Rare CNVs accounted for 1–3% of heritability across diagnoses. In ASD, associations were uniformly positive, consistent with autism having diverse etiologies and clinical presentations. By contrast, CNVs showed a dose-dependent relationship for other diagnoses, including SCZ and PTSD, with reciprocal deletions and duplications having inversely correlated effects and distinct genotype-phenotype relationships. Our findings suggest that genes have effects that are both dose-dependent and pleiotropic, such that a positive influence on one dimension of psychopathology may be accompanied by positive or negative effects on others.

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Contrôle bibliographique ouvert

DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.

Titre Crossref: A cross-disorder analysis of CNVs finds novel loci and dose-dependent relationships of genes to psychiatric traits
Date Crossref: 15/07/2025
Éditeur: openRxiv
Type: posted-content

Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude et ne compte pas comme une seconde source scientifique indépendante.

Institutions déclarées

University of California San Diego Radboud University Nijmegen Radboud University Medical Center Hospital for Sick Children SickKids Foundation VA San Diego Healthcare System Centre Hospitalier Universitaire Sainte-Justine Université de Montréal Oslo University Hospital University of Oslo MRC Centre for Regenerative Medicine University of Edinburgh Umeå University Karolinska Institutet Diakonhjemmet Hospital Stockholm Health Care Services Columbia University Dalhousie University National Institute of Mental Health Virginia Commonwealth University TUM Klinikum Technical University of Munich Universitat Autònoma de Barcelona Vall d'Hebron Institut de Recerca Vall d'Hebron Hospital Universitari Universitat de Barcelona Boston Children's Hospital Harvard University Boston Children's Museum University College London The University of Melbourne University of Münster Florey Institute of Neuroscience and Mental Health FH Münster Goethe University Frankfurt University Hospital Frankfurt Mayo Clinic WinnMed Mayo Clinic in Florida State University of New York SUNY Downstate Health Sciences University Centre for Mental Health Cardiff University Heidelberg University University Hospital Heidelberg University Medical Center Utrecht King's College London Max Planck Institute of Psychiatry UNSW Sydney University of North Carolina at Chapel Hill Icahn School of Medicine at Mount Sinai Hunter Medical Research Institute University of Newcastle Australia National Institute of Health Dr. Ricardo Jorge University of Cape Town Inserm Monash University University of Lausanne Université Paris Cité Institut de Psychiatrie et Neurosciences de Paris University of Bonn University Hospital Bonn Centre National de la Recherche Scientifique Sorbonne Université Assistance Publique – Hôpitaux de Paris Pitié-Salpêtrière Hospital Institut Systèmes Intelligents et de Robotique Trinity College Dublin University of Toronto Bielefeld University Kent State University University Hospital Schleswig-Holstein University of Lübeck University of California, San Francisco Pierre Fabre (France)Sheppard Pratt Health System University of Freiburg University Medical Center Freiburg Cheshire West and Chester Hospital of Southern Norway Neurosciences Institute Stanford University Indiana University – Purdue University Indianapolis University of Tartu SUNY Upstate Medical University Case Western Reserve University Philipps University of Marburg University of Basel University Hospital of Basel Mayo Clinic in Arizona Janssen (Belgium)Janssen (United States)Neuroscience Research Australia Ufa Institute of Chemistry Russian Medical Academy of Continuous Professional Education Bashkir State Medical University Kemerovo State University Universitätsmedizin Greifswald University of Chicago University of California, Los Angeles Comprehensive Cancer Center Vienna Medical University of Vienna Children's Hospital of Philadelphia University of Pennsylvania Johns Hopkins University Johns Hopkins Medicine University of Worcester New South Wales Department of Health VA Greater Los Angeles Healthcare System Spitalul Clinic de Psihiatrie Alexandru Obregia Instituto de Investigación Biomédica de Málaga University of Bergen VA Palo Alto Health Care System Medical Research Council University of Peshawar Institute of Genetics and Cancer Essen University Hospital University of Duisburg-Essen Western Cape Department of Health Stellenbosch University Mental Health Services Copenhagen University Hospital Universidade Federal de São Paulo Fujita Health University University of Gothenburg McLean Hospital Centre for Addiction and Mental Health Institute for Behavioral Medicine The Ohio State University Brain (Germany)Haukeland University Hospital Rutgers, The State University of New Jersey Environmental and Occupational Health Sciences Institute Westmead Institute for Medical Research Hôpital Armand-Trousseau Maladies génétiques d’expression pédiatrique Texas A&M University Bryan College Neurobehavioral Systems University of Manitoba New York University QIMR Berghofer Medical Research Institute Harvard University Press University of Massachusetts Boston University of North Carolina Health Care Queensland University of Technology The University of Queensland Central Institute of Mental Health Alexandrovska Hospital Universidad de Granada Instituto de Investigación Biosanitaria de Granada Park Centre for Mental Health HolsboerMaschmeyer NeuroChemie (Germany)Northern Illinois University Broad Institute University of Helsinki Massachusetts General Hospital Institute for Molecular Medicine Finland Poznan University of Medical Sciences Oxford Health NHS Foundation Trust Emory University LMU Klinikum Institut für Psychiatrische Phänomik und Genomik Ludwig-Maximilians-Universität München University of Michigan National Cancer Institute Division of Cancer Epidemiology and Genetics University of Aberdeen Royal Cornhill Hospital South African Medical Research Council German Center for Diabetes Research Délégation Paris 5 Sorbonne Paris Cité Hôpital Cochin Ministry of Health of the Russian Federation University Psychiatric Hospital Louisiana State University Health Sciences Center New Orleans University of South Florida Florida College University of California, Irvine New York Psychoanalytic Society and Institute New York State Psychiatric Institute Universidade Nova de Lisboa Stanley Foundation University of the Sunshine Coast University of Washington

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Sujets associés

Genomic variations and chromosomal abnormalitiesGenetics and Neurodevelopmental DisordersGenetic Associations and Epidemiology

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