| Title: | Genome-wide meta-analysis of quantitatively measured generalized anxiety symptoms in individuals of European ancestry |
| Journal: | Nature Human Behaviour |
| Published: | 9 Jun 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/42265330/ |
| DOI: | https://doi.org/10.1038/s41562-026-02476-7 |
| URL: | https://www.nature.com/articles/s41562-026-02476-7.pdf |
Publication 20745
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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.</p>
53 Authors
- Megan Skelton
- Brittany L. Mitchell
- Elham Assary
- Danyang Li
- Genevieve Morneau-Vaillancourt
- Alan E. Murphy
- Abigail R. ter Kuile
- Rujia Wang
- Mark J. Adams
- Enda M. Byrne
- Elizabeth C. Corfield
- Poppy Z. Grimes
- Laurie J. Hannigan
- Jihua Hu
- Kadri Kõiv
- Alex S. F. Kwong
- Sergi Papiol
- Johanne H. Pettersen
- Giorgio Pistis
- Enrique Castelao
- Nora I. Strom
- Peter J. van der Most
- Ole A. Andreassen
- Angelika Erhardt-Lehmann
- Alexandra Havdahl
- Nathan Skene
- Brad Verhulst
- Heike Weber
- Chérie Armour
- Helga Ask
- William E. Copeland
- Udo Dannlowski
- Jürgen Deckert
- Katharina Domschke
- Ian B. Hickie
- Kelli Lehto
- Tina B. Lonsdorf
- Ulrike Lueken
- Michelle K. Lupton
- Sarah E. Medland
- Andrew M. McIntosh
- Albertine J. Oldehinkel
- Martin Preisig
- Andreas Reif
- Harold Snieder
- James T. R. Walters
- Naomi R. Wray
- Catharina A. Hartman
- Nicholas G. Martin
- John M. Hettema
- Gerome Breen
- Jonathan R. I. Coleman
- Thalia C. Eley
1 Application
| Application ID | Title |
|---|---|
| 82087 | Genetics and genetic epidemiology of brain-related traits and disorders, and their interplay with physical health |
Enabling scientific discoveries that improve human health