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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PMID
42265330
TITLE
Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry.
ABSTRACT
Anxiety is heritable and exists on a continuum, with symptoms ranging from adaptive threat response to clinical disorder. Here we performed a genome-wide association meta-analysis of generalized anxiety symptom severity in 693,869 individuals of European ancestry from 14 cohorts. We identified 80 independent genome-wide significant variants within 74 loci, 39 of which were newly associated with anxiety. SNP-based heritability was 5.9% (posterior s.d. = 0.15%). Polygenic scores were significantly associated with anxiety symptom severity and disorder in European, African and South Asian ancestry samples (R  = 1.2-2.9%). Significant genetic correlations (r ) were estimated with mental and physical health traits, including case-control anxiety, neuroticism and depression (r  = 0.71-0.85), irritable bowel syndrome (r  = 0.57), coronary artery disease, endometriosis and migraine (r  = 0.20-0.27). Gene-based and pathway analyses implicated synaptic and axonal processes, with enriched expression in the brain. These findings highlight the discovery power gained from analysing a quantitative trait rather than a case-control phenotype in anxiety genetics.
© 2026. The Author(s).
DATE PUBLISHED
2026 Jun 09
HISTORY
PUBSTATUS PUBSTATUSDATE
received 2025/07/08
accepted 2026/04/13
medline 2026/06/10 06:54
pubmed 2026/06/10 06:54
entrez 2026/06/09 23:27
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Skelton M Skelton Megan M Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Mitchell BL Mitchell Brittany L BL School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Assary E Assary Elham E Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Li D Li Danyang D Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Morneau-Vaillancourt G Morneau-Vaillancourt Genevieve G Research Centre of the Montreal University Institute of Mental Health, University of Montreal, Montreal, Quebec, Canada.
Murphy AE Murphy Alan E AE Department of Brain Sciences, Imperial College London, London, UK.
Ter Kuile AR Ter Kuile Abigail R AR Department of Clinical, Educational, and Health Psychology, University College London, London, UK.
Wang R Wang Rujia R National Institute for Health and Care Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
Adams MJ Adams Mark J MJ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Byrne EM Byrne Enda M EM The University of Queensland, Child Health Research Centre, Brisbane, Queensland, Australia.
Corfield EC Corfield Elizabeth C EC MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, UK.
Grimes PZ Grimes Poppy Z PZ Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Hannigan LJ Hannigan Laurie J LJ Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Hu J Hu Jihua J School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Kõiv K Kõiv Kadri K Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Kwong ASF Kwong Alex S F ASF Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Papiol S Papiol Sergi S Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain.
Pettersen JH Pettersen Johanne H JH PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
Pistis G Pistis Giorgio G Department of Psychiatry, Lausanne University Hospital (CHUV) and University of Lausanne, Prilly, Switzerland.
Castelao E Castelao Enrique E Department of Psychiatry, Lausanne University Hospital (CHUV) and University of Lausanne, Prilly, Switzerland.
Strom NI Strom Nora I NI Department of Biomedicine, Aarhus University, Aarhus, Denmark.
van der Most PJ van der Most Peter J PJ Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Anxiety Disorders Working Group of the Psychiatric Genomics Consortium
GLAD+ authors
Lifelines Cohort Study
NIHR BioResource
PROTECT-AD Consortium
Andreassen OA Andreassen Ole A OA Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Erhardt-Lehmann A Erhardt-Lehmann Angelika A Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
Havdahl A Havdahl Alexandra A PROMENTA Research Centre, Department of Psychology, University of Oslo, Oslo, Norway.
Skene N Skene Nathan N Department of Brain Sciences, Imperial College London, London, UK.
Verhulst B Verhulst Brad B Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA.
Weber H Weber Heike H Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Würzburg, Germany.
Armour C Armour Chérie C Stress, Trauma and Related Conditions Research Centre (STARC), School of Psychology, Queen's University Belfast, Belfast, UK.
Ask H Ask Helga H PsychGen Centre for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.
Copeland WE Copeland William E WE Department of Psychiatry, University of Vermont, Burlington, VT, USA.
Dannlowski U Dannlowski Udo U Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Site Jena Magdeburg Halle, Jena, Germany.
Deckert J Deckert Jürgen J Institute of Clinical Epidemiology and Biometrics, University of Würzburg, Würzburg, Germany.
Domschke K Domschke Katharina K German Center for Mental Health (DZPG), Partner Site Berlin-Potsdam, Berlin, Germany.
Hickie IB Hickie Ian B IB Brain and Mind Centre, The University of Sydney, Sydney, New South Wales, Australia.
Lehto K Lehto Kelli K Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia.
Lonsdorf TB Lonsdorf Tina B TB Psychology, Biological Psychology and Cognitive Neuroscience, University of Bielefeld, Bielefeld, Germany.
Lueken U Lueken Ulrike U German Center for Mental Health (DZPG), Partner Site Berlin-Potsdam, Berlin, Germany.
Lupton MK Lupton Michelle K MK School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia.
Medland SE Medland Sarah E SE School of Psychology and Counselling, Queensland University of Technology, Brisbane, Queensland, Australia.
McIntosh AM McIntosh Andrew M AM Division of Psychiatry, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Oldehinkel AJ Oldehinkel Albertine J AJ Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Preisig M Preisig Martin M Department of Psychiatry, Lausanne University Hospital (CHUV) and University of Lausanne, Prilly, Switzerland.
Reif A Reif Andreas A Fraunhofer Institute for Translational Medicine and Pharmacology ITMP, Frankfurt am Main, Germany.
Snieder H Snieder Harold H Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Walters JTR Walters James T R JTR National Centre for Mental Health and Centre for Neuropsychiatric Genetics and Genomics, Cardiff University, Cardiff, UK.
Wray NR Wray Naomi R NR Department of Psychiatry, University of Oxford, Oxford, UK.
Hartman CA Hartman Catharina A CA Department of Psychiatry, Interdisciplinary Center Psychopathology and Emotion Regulation, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
Martin NG Martin Nicholas G NG School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Hettema JM Hettema John M JM Department of Psychiatry and Behavioral Sciences, Texas A&M University, Bryan, TX, USA.
Breen G Breen Gerome G National Institute for Health and Care Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
Coleman JRI Coleman Jonathan R I JRI National Institute for Health and Care Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
Eley TC Eley Thalia C TC National Institute for Health and Care Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK. thalia.eley@kcl.ac.uk.
INVESTIGATORS
LASTNAME FORENAME INITIALS AFFILIATION
Wittchen Uli U
Pittig Andre A
Heinig Ingmar I
Hoyer Jürgen J
Fydrich Thomas T
Hamm Alfons A
Richter Jan J
Arolt Volker V
Kölkebeck Katja K
Schneider Sylvia S
Margraf Jürgen J
Straube Benjamin B
Rief Winfried W
Pauli Paul P
Neudeck Peter P
JOURNAL
VOLUME:
ISSUE:
TITLE: Nature human behaviour
ISOABBREVIATION: Nat Hum Behav
YEAR: 2026
MONTH: Jun
DAY: 09
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 2397-3374
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Nat Hum Behav
COUNTRY: England
ISSNLINKING: 2397-3374
NLMUNIQUEID: 101697750
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
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MR/V012878/1 RCUK | Medical Research Council (MRC)
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