Rare copy number variation in posttraumatic stress disorder.

Autor:	Maihofer AX; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA. amaihofer@health.ucsd.edu.; Department of Family Medicine and Public Health, University of California San Diego, La Jolla, CA, USA. amaihofer@health.ucsd.edu.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA. amaihofer@health.ucsd.edu., Engchuan W; The Hospital for Sick Children, Genetics and Genome Biology, Toronto, Ontario, Canada.; The Hospital for Sick Children, The Centre for Applied Genomics, Toronto, Ontario, Canada., Huguet G; Centre Hospitalier Universitaire Sainte-Justine Centre de Recherche, Montreal, Quebec, Canada., Klein M; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA., MacDonald JR; The Hospital for Sick Children, Genetics and Genome Biology, Toronto, Ontario, Canada., Shanta O; Bioinformatics and Systems Biology Graduate Program, University of California San Diego, La Jolla, CA, USA., Thiruvahindrapuram B; The Hospital for Sick Children, Genetics and Genome Biology, Toronto, Ontario, Canada., Jean-Louis M; Department of Pediatrics, Centre Hospitalier Universitaire Sainte-Justine Centre de Recherche, Montreal, Quebec, Canada., Saci Z; Centre Hospitalier Universitaire Sainte-Justine Centre de Recherche, Montreal, Quebec, Canada., Jacquemont S; Centre Hospitalier Universitaire Sainte-Justine Centre de Recherche, Montreal, Quebec, Canada.; Department of Genetics, Centre Hospitalier Universitaire Vaudois, Lausanne, Vaud, Switzerland.; Department of Pediatrics, University of Montreal, Montreal, Quebec, Canada., Scherer SW; The Hospital for Sick Children, Genetics and Genome Biology, Toronto, Ontario, Canada.; University of Toronto, McLaughlin Centre, Toronto, Ontario, Canada.; Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada., Ketema E; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA., Aiello AE; Department of Epidemiology, Robert N Butler Columbia Aging Center, Columbia University, New York, NY, USA., Amstadter AB; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA., Avdibegović E; Department of Psychiatry, University Clinical Center of Tuzla, Tuzla, Bosnia and Herzegovina., Babic D; Department of Psychiatry, University Clinical Center of Mostar, Mostar, Bosnia and Herzegovina., Baker DG; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA., Bisson JI; MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, National Centre for Mental Health, Cardiff, South Glamorgan, UK., Boks MP; Department of Psychiatry, UMC Utrecht Brain Center, Utrecht, the Netherlands., Bolger EA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Bryant RA; Department of Psychology, University of New South Wales, Sydney, NSW, Australia., Bustamante AC; Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, USA., Caldas-de-Almeida JM; CEDOC-Chronic Diseases Research Centre, Lisbon Institute of Global Mental Health, Lisbon, Portugal., Cardoso G; Lisbon Institute of Global Mental Health and Comprehensive Health Research Centre, Universidade Nova de Lisboa, Lisboa, Portugal., Deckert J; University Hospital of Wuerzburg, Center of Mental Health, Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, Germany., Delahanty DL; Department of Psychological Sciences, Kent State University, Kent, OH, USA.; Research and Sponsored Programs, Kent State University, Kent, OH, USA., Domschke K; Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, Freiburg, Germany.; Faculty of Medicine, Centre for Basics in Neuromodulation, University of Freiburg, Freiburg, Germany., Dunlop BW; Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA., Dzubur-Kulenovic A; Department of Psychiatry, University Clinical Center of Sarajevo, Sarajevo, Bosnia and Herzegovina., Evans A; MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, National Centre for Mental Health, Cardiff, South Glamorgan, UK., Feeny NC; Department of Psychological Sciences, Case Western Reserve University, Cleveland, OH, USA., Franz CE; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA., Gautam A; Walter Reed Army Institute of Research, Medical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Silver Spring, MD, USA., Geuze E; Netherlands Ministry of Defence, Brain Research and Innovation Centre, Utrecht, the Netherlands.; Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands., Goci A; Department of Psychiatry, University Clinical Centre of Kosovo, Prishtina, Kosovo., Hammamieh R; Walter Reed Army Institute of Research, Medical Readiness Systems Biology, Center for Military Psychiatry and Neuroscience, Silver Spring, MD, USA., Jakovljevic M; Department of Psychiatry, University Hospital Center of Zagreb, Zagreb, Croatia., Jett M; US Medical Research & Development Comm, Fort Detrick, MD, USA.; Walter Reed Army Institute of Research, Headquarter, Silver Spring, MD, USA., Jones I; MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, National Centre for Mental Health, Cardiff, South Glamorgan, UK., Kaufman ML; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Kessler RC; Department of Health Care Policy, Harvard Medical School, Boston, MA, USA., King AP; Ohio State University, College of Medicine, Institute for Behavioral Medicine Research, Columbus, OH, USA., Kremen WS; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA., Lawford BR; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia., Lebois LAM; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Lewis C; MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, National Centre for Mental Health, Cardiff, South Glamorgan, UK., Liberzon I; Department of Psychiatry and Behavioral Sciences, Texas A&M University College of Medicine, Bryan, TX, USA., Linnstaedt SD; Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA., Lugonja B; MRC Centre for Psychiatric Genetics and Genomics, Cardiff University, National Centre for Mental Health, Cardiff, South Glamorgan, UK., Luykx JJ; Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands.; Department of Translational Neuroscience, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands., Lyons MJ; Department of Psychological & Brain Sciences, Boston University, Boston, MA, USA., Mavissakalian MR; Department of Psychiatry, University Hospitals, Cleveland, OH, USA., McLaughlin KA; Department of Psychology, Harvard University, Boston, MA, USA., McLean SA; Institute for Trauma Recovery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.; Department of Emergency Medicine, UNC Institute for Trauma Recovery, Chapel Hill, NC, USA., Mehta D; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia.; Queensland University of Technology, Centre for Genomics and Personalised Health, Kelvin Grove, QLD, Australia., Mellor R; Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Greenslopes, QLD, Australia., Morris CP; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia., Muhie S; Walter Reed Army Institute of Research, Silver Spring, MD, USA., Orcutt HK; Department of Psychology, Northern Illinois University, DeKalb, IL, USA., Peverill M; Department of Psychology, University of Washington, Seattle, WA, USA., Ratanatharathorn A; Department of Epidemiology, Columbia University Mailmain School of Public Health, New York, NY, USA.; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA., Risbrough VB; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA., Rizzo A; University of Southern California, Institute for Creative Technologies, Los Angeles, CA, USA., Roberts AL; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA., Rothbaum AO; Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, SC, USA., Rothbaum BO; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA., Roy-Byrne P; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA., Ruggiero KJ; Department of Nursing and Department of Psychiatry, Medical University of South Carolina, Charleston, SC, USA., Rutten BPF; Department of Psychiatry and Neuropsychology, Maastricht Universitair Medisch Centrum, School for Mental Health and Neuroscience, Maastricht, Limburg, the Netherlands., Schijven D; Department of Psychiatry, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands.; Department of Translational Neuroscience, UMC Utrecht Brain Center Rudolf Magnus, Utrecht, the Netherlands., Seng JS; University of Michigan, School of Nursing, Ann Arbor, MI, USA.; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA.; Department of Women's and Gender Studies, University of Michigan, Ann Arbor, MI, USA.; University of Michigan, Institute for Research on Women and Gender, Ann Arbor, MI, USA., Sheerin CM; Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Richmond, VA, USA., Sorenson MA; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA., Teicher MH; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; Developmental Biopsychiatry Research Program, McLean Hospital, Belmont, MA, USA., Uddin M; Genomics Program, College of Public Health, University of South Florida, Tampa, FL, USA., Ursano RJ; Department of Psychiatry, Uniformed Services University, Bethesda, MD, USA., Vinkers CH; Amsterdam Neuroscience, Mood, Anxiety, Psychosis, Sleep & Stress Program, Amsterdam, the Netherlands.; Department of Psychiatry, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.; Department of Anatomy and Neurosciences, Amsterdam UMC Location Vrije Universiteit Amsterdam, Amsterdam, the Netherlands., Voisey J; School of Biomedical Sciences, Queensland University of Technology, Kelvin Grove, QLD, Australia.; Queensland University of Technology, Centre for Genomics and Personalised Health, Kelvin Grove, QLD, Australia., Weber H; University Hospital of Wuerzburg, Center of Mental Health, Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, Germany., Winternitz S; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA., Xavier M; Universidade Nova de Lisboa, Nova Medical School, Lisboa, Portugal., Yang R; Walter Reed Army Institute of Research, Silver Spring, MD, USA., McD Young R; Queensland University of Technology, School of Clinical Sciences, Kelvin Grove, QLD, Australia.; University of the Sunshine Coast, The Chancellory, Sippy Downs, QLD, Australia., Zoellner LA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA., Salem RM; University of California San Diego, Herbert Wertheim School of Public Health and Human Longevity Science, La Jolla, CA, USA., Shaffer RA; Department of Epidemiology and Health Sciences, Naval Health Research Center, San Diego, CA, USA., Wu T; Division of Epidemiology and Biostatistics, San Diego State University, School of Public Health, San Diego, CA, USA.; University of California, San Diego, Moores Cancer Center, San Diego, CA, USA., Ressler KJ; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.; McLean Hospital, Belmont, MA, USA.; Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA, USA., Stein MB; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Psychiatry Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.; University of California San Diego, School of Public Health, La Jolla, CA, USA., Koenen KC; Broad Institute of MIT and Harvard, Stanley Center for Psychiatric Research, Cambridge, MA, USA.; Department of Epidemiology, Harvard T. H. School of Public Health, Boston, MA, USA.; Psychiatric and Neurodevelopmental Genetics Unit (PNGU), Massachusetts General Hospital, Boston, MA, USA., Sebat J; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.; Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA., Nievergelt CM; Department of Psychiatry, University of California San Diego, La Jolla, CA, USA.; Veterans Affairs San Diego Healthcare System, Center of Excellence for Stress and Mental Health, San Diego, CA, USA.; Research Service, Veterans Affairs San Diego Healthcare System, San Diego, CA, USA.
Jazyk:	angličtina
Zdroj:	Molecular psychiatry [Mol Psychiatry] 2022 Dec; Vol. 27 (12), pp. 5062-5069. Date of Electronic Publication: 2022 Sep 21.
DOI:	10.1038/s41380-022-01776-4
Abstrakt:	Posttraumatic stress disorder (PTSD) is a heritable (h 2  = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10 -8 ). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further. (© 2022. The Author(s).)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu Full text from SpringerLink