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Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; National Institute for Health and Care Research Maudsley Biomedical Research Centre, South London and Maudsley NHS Trust, London, UK.
Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. (Anxiety Disorders Working Group of the Psychiatric Genomics Consortium)ORCID iD: 0000-0002-4811-2330
Örebro University, School of Medical Sciences. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. (Anxiety Disorders Working Group of the Psychiatric Genomics Consortium)ORCID iD: 0000-0002-6851-3297
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Number of Authors: 532026 (English)In: Nature Human Behaviour, E-ISSN 2397-3374, Vol. 10, no 8, p. 1594-1608Article in journal (Refereed) Published
Abstract [en]

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 (R2 = 1.2-2.9%). Significant genetic correlations (rg) were estimated with mental and physical health traits, including case-control anxiety, neuroticism and depression (rg = 0.71-0.85), irritable bowel syndrome (rg = 0.57), coronary artery disease, endometriosis and migraine (rg = 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.

Place, publisher, year, edition, pages
Nature Portfolio, 2026. Vol. 10, no 8, p. 1594-1608
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Psychiatry
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URN: urn:nbn:se:oru:diva-129376DOI: 10.1038/s41562-026-02476-7PubMedID: 42265330OAI: oai:DiVA.org:oru-129376DiVA, id: diva2:2070010
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Available from: 2026-06-11 Created: 2026-06-11 Last updated: 2026-08-25Bibliographically approved

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Garcia-Argibay, MiguelLarsson, Henrik

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