Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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39006447
TITLE
Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.
ABSTRACT
The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder, and phobias) are highly prevalent, often onset early, persist throughout life, and cause substantial global disability. Although distinct in their clinical presentations, they likely represent differential expressions of a dysregulated threat-response system. Here we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant ANX risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 of the 58 associated variants were replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism, and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism underlying ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.
DATE PUBLISHED
2024 Jul 05
HISTORY
PUBSTATUS PUBSTATUSDATE
pubmed 2024/07/15 06:42
medline 2024/07/15 06:43
entrez 2024/07/15 05:31
pmc-release 2024/07/12
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Strom NI Strom Nora I NI Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Verhulst B Verhulst Brad B Psychiatry and Behavioral Sciences, Texas A&M University, College Station, Texas, USA.
Bacanu SA Bacanu Silviu-Alin SA Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA.
Cheesman R Cheesman Rosa R PROMENTA Centre, Department of Psychology, University of Oslo, Oslo, Norway.
Purves KL Purves Kirstin L KL Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Gedik H Gedik Hüseyin H Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
Mitchell BL Mitchell Brittany L BL Faculty of Medicine, Queensland University , Brisbane, Queensland, Australia.
Kwong AS Kwong Alex S AS Centre for Clinical Brain Sciences, Division of Psychiatry, University of Edinburgh, Edinburgh, UK.
Faucon AB Faucon Annika B AB Division of Medicine, Human Genetics, Vanderbilt University, Nashville, Tennessee, USA.
Singh K Singh Kritika K Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Medland S Medland Sarah S Brain and Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Colodro-Conde L Colodro-Conde Lucia L School of Psychology, The University of Queensland, Brisbane, Queensland, Australia.
Krebs K Krebs Kristi K Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Hoffmann P Hoffmann Per P Department of Biomedicine, Human Genomics Research Group, University of Basel; University Hospital Basel, Basel, Switzerland.
Herms S Herms Stefan S Department of Biomedicine, Human Genomics Research Group, University of Basel; University Hospital Basel, Basel, Switzerland.
Gehlen J Gehlen Jan J Center for Human Genetics, University of Marburg, Marburg, Germany.
Ripke S Ripke Stephan S Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts, USA.
Awasthi S Awasthi Swapnil S Dept. of Psychiatry and Psychotherapy, Charité - Universitätsmedizin, Berlin, Germany.
Palviainen T Palviainen Teemu T Helsinki Institute of Life Science, Institute for Molecular Medicine Finland - FIMM, University of Helsinki, Helsinki, Finland.
Tasanko EM Tasanko Elisa M EM Faculty of Medicine, Department of Psychology and Logopedics, SleepWell Research Program, University of Helsinki, Helsinki, Finland.
Peterson RE Peterson Roseann E RE Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA.
Adkins DE Adkins Daniel E DE School of Medicine, Department of Psychiatry, University of Utah, Salt Lake City, Utah, USA.
Shabalin AA Shabalin Andrey A AA School of Medicine, Department of Psychiatry, University of Utah, Salt Lake City, Utah, USA.
Adams MJ Adams Mark J MJ Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Iveson MH Iveson Matthew H MH Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Campbell A Campbell Archie A College of Medicine and Veterinary Medicine, Institute of Genetics and Cancer; Centre for Genomic and Experimental Medicine, University of Edinburgh, Edinburgh, UK.
Thomas LF Thomas Laurent F LF Clinic of Laboratory Medicine, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
Winsvold BS Winsvold Bendik S BS Department of Neurology, Oslo University Hospital, Oslo, Norway.
Drange OK Drange Ole Kristian OK Department of Psychiatry, Sørlandet Hospital, Kristiansand, Norway.
Børte S Børte Sigrid S Department of Public Health and Nursing, HUNT Center for Molecular and Clinical Epidemiology, Norwegian University of Science and Technology, Trondheim, Norway.
Ter Kuile AR Ter Kuile Abigail R AR Department of Clinical, Educational and Health Psychology, University College London, London, United Kingdom.
Nguyen TH Nguyen Tan-Hoang TH Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, Virginia, USA.
Meier SM Meier Sandra M SM Psychiatry, Dalhousie University, Halifax, Nova Scotia, Canada.
Corfield EC Corfield Elizabeth C EC Nic Waals Institute , Lovisenberg Diaconal Hospital, Oslo, Norway.
Hannigan L Hannigan Laurie L Bristol Medical School, Population Health Sciences, University of Bristol, Bristol, UK.
Levey DF Levey Daniel F DF Psychiatry, Research, Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut, USA.
Czamara D Czamara Darina D Department of Genes and Environment, Max-Planck Institute of Psychiatry, Munich, Germany.
Weber H Weber Heike H Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
Choi KW Choi Karmel W KW Psychiatry, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
Pistis G Pistis Giorgio G Psychiatric Epidemiology and Psychopathology Research Center, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland.
Couvy-Duchesne B Couvy-Duchesne Baptiste B Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia.
Van der Auwera S Van der Auwera Sandra S Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Teumer A Teumer Alexander A Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Karlsson R Karlsson Robert R Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Garcia-Argibay M Garcia-Argibay Miguel M Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Lee D Lee Donghyung D Department of Statistics, Miami University, Oxford, Ohio, USA.
Wang R Wang Rujia R Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Bjerkeset O Bjerkeset Ottar O Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
Stordal E Stordal Eystein E Department of Mental Health, Norwegian University of Science and Technology, Trondheim, Norway.
Bäckmann J Bäckmann Julia J Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Salum GA Salum Giovanni A GA Child Psychiatry, National Institute of Developmental Psychiatry, São Paulo, Brazil.
Zai CC Zai Clement C CC Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA.
Kennedy JL Kennedy James L JL Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Zai G Zai Gwyneth G Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Tiwari AK Tiwari Arun K AK Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada.
Heilmann-Heimbach S Heilmann-Heimbach Stefanie S Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Schmidt B Schmidt Börge B Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University of Duisburg-Essen, Essen, Germany.
Kaprio J Kaprio Jaakko J Helsinki Institute of Life Science, Institute for Molecular Medicine Finland - FIMM, University of Helsinki, Helsinki, Finland.
Kennedy MM Kennedy Martin M MM Pathology and Biomedical Science, University of Otago, Christchurch, New Zealand.
Boden J Boden Joseph J Psychological Medicine, University of Otago, Christchurch, New Zealand.
Havdahl A Havdahl Alexandra A Bristol Medical School, Population Health Sciences, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Middeldorp CM Middeldorp Christel M CM Child and Youth Mental Health Service, Children's Health Queensland Hospital and Health Service, Brisbane, Queensland, Australia.
Lopes FL Lopes Fabiana L FL Department of Psychiatry and Human Behavior, Alpert Medical School of Brown University, Providence, Rhode Island, USA.
Akula N Akula Nirmala N National Institute of Mental Health, Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health, Bethesda, Maryland, USA.
McMahon FJ McMahon Francis J FJ Psychiatry & Behavioral Sciences, Johns Hopkins University, Baltimore, Maryland, USA.
Binder EB Binder Elisabeth B EB Department of Genes and Environment, Max-Planck Institute of Psychiatry, Munich, Germany.
Fehm L Fehm Lydia L Department of Psychology, Zentrum für Psychotherapie, Humboldt-Universität zu Berlin, Berlin, Germany.
Ströhle A Ströhle Andreas A Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
Castelao E Castelao Enrique E Psychiatric Epidemiology and Psychopathology Research Center, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland.
Tiemeier H Tiemeier Henning H Child and Adolescent Psychiatry, Erasmus University Medical Center, Rotterdam, Netherlands.
Stein DJ Stein Dan J DJ SAMRC Unit on Risk & Resilience in Mental Disorders, Department of Psychiatry & Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Whiteman D Whiteman David D Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Olsen C Olsen Catherine C Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
Fuller Z Fuller Zachary Z 23andMe, Sunnyvale, CA, USA.
Wang X Wang Xin X 23andMe, Sunnyvale, CA, USA.
Wray NR Wray Naomi R NR Department of Psychiatry, University of Oxford, Oxford, UK.
Byrne EM Byrne Enda M EM Child Health Research Centre, University of Queensland, Brisbane, Queensland, Australia.
Lewis G Lewis Glyn G UCL Division of Psychiatry, University College London, London, UK.
Timpson NJ Timpson Nicholas J NJ Bristol Medical School, Population Health Sciences, MRC Integrative Epidemiology Unit, University of Bristol, Bristol, UK.
Davis LK Davis Lea K LK Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Hickie IB Hickie Ian B IB Brain and Mind Centre, University of Sydney, Sydney, Australia.
Gillespie NA Gillespie Nathan A NA Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA.
Milani L Milani Lili L Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Schumacher J Schumacher Johannes J Center for Human Genetics, University of Marburg, Marburg, Germany.
Woldbye DP Woldbye David P DP Department of Neuroscience, Laboratory of Neural Plasticity, University of Copenhagen, Copenhagen, Denmark.
Forstner AJ Forstner Andreas J AJ Center for Human Genetics, University of Marburg, Marburg, Germany.
Nöthen MM Nöthen Markus M MM Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
Hovatta I Hovatta Iiris I Faculty of Medicine, Department of Psychology and Logopedics and SleepWell Research Program, University of Helsinki, Helsinki, Finland.
Horwood J Horwood John J Psychological Medicine, University of Otago, Christchurch, New Zealand.
Copeland WE Copeland William E WE UVM Medical Center, Department of Psychiatry, University of Vermont, Burlington, Vermont, USA.
Maes HH Maes Hermine H HH Massey Cancer Center, Virginia Commonwealth University, Richmond, Virginia, USA.
McIntosh AM McIntosh Andrew M AM Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Andreassen OA Andreassen Ole A OA K. G. Jebsen Center for Neurodevelopmental disorders, University of Oslo, Oslo, Norway.
Zwart JA Zwart John-Anker JA Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Mors O Mors Ole O The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Aarhus University, Aarhus, Denmark.
Børglum AD Børglum Anders D AD Center for Genomics and Personalised Medicine, Aarhus University, Aarhus, Denmark.
Mortensen PB Mortensen Preben B PB The National Centre for Register-based Research, Aarhus University, Aarhus, Denmark.
Ask H Ask Helga H PROMENTA Centre, Department of Psychology, University of Oslo, Oslo, Norway.
Reichborn-Kjennerud T Reichborn-Kjennerud Ted T NORMENT Centre, University of Oslo, Oslo, Norway.
Najman JM Najman Jackob M JM Faculty of Medicine, School of Public Health, University of Queensland, Herston, Queensland, Australia.
Stein MB Stein Murray B MB School of Public Health, University of California San Diego, La Jolla, CA, USA.
Gelernter J Gelernter Joel J Departments of Genetics and Neuroscience, Yale University of Medicine, New Haven, Connecticut, USA.
Milaneschi Y Milaneschi Yuri Y Amsterdam Neuroscience; Amsterdam Public Health, Amsterdam University Medical Center, Amsterdam, Netherlands.
Penninx BW Penninx Brenda W BW Amsterdam Neuroscience; Amsterdam Public Health, Amsterdam University Medical Center, Amsterdam, Netherlands.
Boomsma DI Boomsma Dorret I DI Amsterdam Public Health, Amsterdam University Medical Center, Amsterdam, Netherlands.
Maron E Maron Eduard E Department of Medicine, Centre for Neuropsychopharmacology,, Division of Brain Sciences, Imperial College London, London, UK.
Erhardt-Lehmann A Erhardt-Lehmann Angelika A Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
Rück C Rück Christian C Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Region Stockholm, Stockholm, Sweden.
Kircher TT Kircher Tilo T TT Department of Psychiatry, University of Marburg, Marburg, Germany.
Melzig CA Melzig Christiane A CA Psychology, Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany.
Alpers GW Alpers Georg W GW School of Social Sciences, Department of Psychology, University of Mannheim, Mannheim, Germany.
Arolt V Arolt Volker V Department of Mental Health, Institute for Translational Psychiatry, University of Muenster, Muenster, Germany.
Domschke K Domschke Katharina K German Center for Mental Health (DZPG), Partner Site Berlin, Berlin, Germany.
Smoller JW Smoller Jordan W JW Psychiatry, Center for Precision Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA.
Preisig M Preisig Martin M Psychiatric Epidemiology and Psychopathology Research Center, Department of Psychiatry, Lausanne University Hospital and University of Lausanne, Prilly, Switzerland.
Martin NG Martin Nicholas G NG Brain and Mental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.
Lupton MK Lupton Michelle K MK Faculty of Health, Queensland University of technology, Queensland, Australia.
Luik AI Luik Annemarie I AI Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands.
Reif A Reif Andreas A Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt - Goethe University, Frankfurt, Germany.
Grabe HJ Grabe Hans J HJ Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Larsson H Larsson Henrik H Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Magnusson PK Magnusson Patrik K PK Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Oldehinkel AJ Oldehinkel Albertine J AJ Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Hartman CA Hartman Catharina A CA Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, Netherlands.
Breen G Breen Gerome G Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Docherty AR Docherty Anna R AR Psychiatry, Virginia Commonwealth University, Richmond, Virginia, USA.
Coon H Coon Hilary H School of Medicine, Psychiatry, University of Utah, Salt Lake City, Utah, USA.
Conrad R Conrad Rupert R Department of Psychosomatic Medicine and Psychotherapy, University Hospital Münster, Münster, Germany.
Lehto K Lehto Kelli K Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Million Veteran Program, FinnGen, 23andMe
Deckert J Deckert Jürgen J Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Würzburg, Würzburg, Germany.
Eley TC Eley Thalia C TC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Mattheisen M Mattheisen Manuel M Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU Munich, Munich, Germany.
Hettema JM Hettema John M JM Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, Texas, USA.
INVESTIGATORS
JOURNAL
VOLUME:
ISSUE:
TITLE: medRxiv : the preprint server for health sciences
ISOABBREVIATION: medRxiv
YEAR: 2024
MONTH: Jul
DAY: 05
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
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MEDLINE JOURNAL
MEDLINETA: medRxiv
COUNTRY: United States
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NLMUNIQUEID: 101767986
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