Skelton, Megan, Mitchell, Brittany L., Assary, Elham, Li, Danyang, Morneau-Vaillancourt, Genevieve and Walters, James T. R.  ORCID: https://orcid.org/0000-0002-6980-4053
2026.
Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry.
Nature Human Behaviour
10
, pp. 1594-1608.
10.1038/s41562-026-02476-7
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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 (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.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Medicine |
| Additional Information: | For full list of authors see https://doi.org/10.1038/s41562-026-02476-7 |
| Publisher: | Nature Research |
| ISSN: | 2397-3374 |
| Date of First Compliant Deposit: | 22 May 2026 |
| Date of Acceptance: | 13 April 2026 |
| Last Modified: | 03 Sep 2026 11:29 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/187174 |
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