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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41634414
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 and cause substantial global disability. Although distinct in their clinical presentations, they probably 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 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 out of the 58 associations 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 implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.
© 2026. The Author(s).
DATE PUBLISHED
2026 Feb
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2024/07/22
accepted 2025/12/12
medline 2026/02/13 01:26
pubmed 2026/02/04 05:06
entrez 2026/02/03 23:33
pmc-release 2026/02/03
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Strom NI Strom Nora I NI Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Verhulst B Verhulst Brad B Psychiatry and Behavioral Sciences, Texas A&M University, College Station, TX, USA.
Bacanu SA Bacanu Silviu-Alin SA Psychiatry, Virginia Commonwealth University, Richmond, VA, 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, VA, 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, TN, USA.
Singh K Singh Kritika K Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, 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 Institute of Medical Genetics and Pathology, Medical Faculty, 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, MA, USA.
Awasthi S Awasthi Swapnil S Department 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 Institute for Genomics in Health, Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Health Sciences University, Brooklyn, NY, USA.
Adkins DE Adkins Daniel E DE School of Medicine, Department of Psychiatry, University of Utah, Salt Lake City, UT, USA.
Shabalin AA Shabalin Andrey A AA School of Medicine, Department of Psychiatry, University of Utah, Salt Lake City, UT, 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 Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Ter Kuile AR Ter Kuile Abigail R AR Department of Clinical, Educational and Health Psychology, University College London, London, UK.
Naamanka J Naamanka Joonas J SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Nguyen TH Nguyen Tan-Hoang TH Human and Molecular Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, 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, CT, 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, MA, 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 Institute for Community Medicine, 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 School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Lee D Lee Donghyung D Department of Statistics, Miami University, Oxford, OH, 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 Faculty of Nursing and Health Science, Nord University, Levanger, Norway.
Stordal E Stordal Eystein E Department of Psychiatry, Hospital Namsos, Nord-Trøndelag Health Trustt, Namsos, Norway.
Bäckman J Bäckman 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, 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, RI, USA.
Akula N Akula Nirmala N National Institute of Mental Health, Genetic Basis of Mood and Anxiety Disorders, National Institutes of Health, Bethesda, MA, USA.
McMahon FJ McMahon Francis J FJ Psychiatry & Behavioral Sciences, Johns Hopkins University, Baltimore, MA, 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, University of Bristol, Bristol, UK.
Davis LK Davis Lea K LK Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Hickie IB Hickie Ian B IB Brain and Mind Centre, University of Sydney, Sydney, New South Wales, Australia.
Gillespie NA Gillespie Nathan A NA Psychiatry, Virginia Commonwealth University, Richmond, VA, 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 Institute of Neuroscience and Medicine (INM-1), Research Center Jülich, Jülich, 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, VT, USA.
Maes HH Maes Hermine H HH Massey Cancer Center, Virginia Commonwealth University, Richmond, VA, 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 PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
Reichborn-Kjennerud T Reichborn-Kjennerud Ted T PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, 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, CT, USA.
Milaneschi Y Milaneschi Yuri Y Amsterdam Neuroscience; Amsterdam Public Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Penninx BW Penninx Brenda W BW Amsterdam Neuroscience; Amsterdam Public Health, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Boomsma DI Boomsma Dorret I DI Amsterdam Public Health, Amsterdam University Medical Center, Amsterdam, The 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, Center of Mental Health, 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, Psychiatric and Neurodevelopmental Genetics Unit, Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, 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, Brisbane, Queensland, Australia.
Luik AI Luik Annemarie I AI Epidemiology, Erasmus University Medical Center, Rotterdam, The 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 School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, 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, The Netherlands.
Hartman CA Hartman Catharina A CA Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen, Groningen, The 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 School of Medicine, Psychiatry; Huntsman Mental Health Institute, University of Utah, Salt Lake City, UT, USA.
Coon H Coon Hilary H School of Medicine, Psychiatry, University of Utah, Salt Lake City, UT, 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.
Veterans Affairs Million Veteran Program
FinnGen
23andMe Research Team
Deckert J Deckert Jürgen J Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital Würzburg, Würzburg, Germany. deckert_j@ukw.de.
Eley TC Eley Thalia C TC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK. thalia.eley@kcl.ac.uk.
Mattheisen M Mattheisen Manuel M Computer Science, Dalhousie University, Halifax, Nova Scotia, Canada. manuel.mattheisen@dal.ca.
Hettema JM Hettema John M JM Psychiatry and Behavioral Sciences, Texas A&M University, College Station, TX, USA. hettema@tamu.edu.
INVESTIGATORS
JOURNAL
VOLUME: 58
ISSUE: 2
TITLE: Nature genetics
ISOABBREVIATION: Nat Genet
YEAR: 2026
MONTH: Feb
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1546-1718
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Genet
COUNTRY: United States
ISSNLINKING: 1061-4036
NLMUNIQUEID: 9216904
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
UpdateOf medRxiv. 2024 Jul 05:2024.07.03.24309466. doi: 10.1101/2024.07.03.24309466. 39006447
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GRANTID AGENCY COUNTRY
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RC2 MH089951 NIMH NIH HHS United States
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KNAW PAH/6635 Koninklijke Nederlandse Akademie van Wetenschappen (Royal Netherlands Academy of Arts and Sciences)
#274611 Norges Forskningsråd (Research Council of Norway)
R01 MH118239 NIMH NIH HHS United States
UL1 TR000445 NCATS NIH HHS United States
5R01MH124847 U.S. Department of Health & Human Services NIH National Institute of Mental Health (NIMH)
R01MH045268, R01MH068521 U.S. Department of Health & Human Services NIH National Institute of Mental Health (NIMH)
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APP2017176 Department of Health National Health and Medical Research Council (NHMRC)
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GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Humans
Genome-Wide Association Study
Anxiety Disorders genetics
White People genetics
Genetic Predisposition to Disease genetics
Polymorphism, Single Nucleotide genetics
Female genetics
Signal Transduction genetics
Male genetics
Case-Control Studies genetics
gamma-Aminobutyric Acid metabolism
Phenotype metabolism
Adult metabolism
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
56-12-2 gamma-Aminobutyric Acid
OTHER ID's
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