Genome-wide insights into generalised anxiety using a dimensional symptom severity approach Article Swipe
Megan Skelton
,
Brittany L. Mitchell
,
Elham Assary
,
Danyang Li
,
Geneviève Morneau‐Vaillancourt
,
Alan E Murphy
,
Abigail ter Kuile
,
Ying Wang
,
Mark J. Adams
,
Enda M. Byrne
,
Elizabeth C. Corfield
,
P Grimes
,
Laurie J. Hannigan
,
Jihua Hu
,
Kadri Kõiv
,
Alex S. F. Kwong
,
Sergi Papiol
,
Johanne Hagen Pettersen
,
Giorgio Pistis
,
Enrique Castelao
,
Nora I. Strom
,
Peter J. van der Most
,
Ole A. Andreassen
,
Angelika Erhardt
,
Alexandra Havdahl
,
Nathan Skene
,
Brad Verhulst
,
Heike Weber
,
Chérie Armour
,
Helga Ask
,
William 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 Walters
,
Naomi R. Wray
,
Catharina A. Hartman
,
Nicholas G. Martin
,
John M. Hettema
,
Gerome Breen
,
Jonathan R. I. Coleman
,
Thalia C. Eley
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.10.25331321
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1101/2025.07.10.25331321
We performed a genome-wide association meta-analysis of generalised anxiety symptom severity in 696,563 individuals of European ancestry from 14 cohorts. We identified 82 independent genome-wide significant variants within 76 loci, 41 of which were novel for anxiety. SNP-based heritability was 5.9% (SE = 0.19%). Polygenic scores were significantly associated with anxiety symptom severity and disorder in European, African, and South Asian ancestry samples (r2=1.2%-3.4%). Significant genetic correlations were estimated with numerous mental and physical health traits, including case-control anxiety, neuroticism and depression (rg=0.71-0.86), 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 additional value of a dimensional approach in anxiety genetics.
Related Topics
Concepts
Anxiety
Neuroticism
Genome-wide association study
Heritability
Depression (economics)
Irritable bowel syndrome
SNP
Clinical psychology
Genetic association
Medicine
Psychiatry
Psychology
Genetics
Gene
Single-nucleotide polymorphism
Biology
Personality
Genotype
Macroeconomics
Economics
Social psychology
Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.1101/2025.07.10.25331321
- https://www.medrxiv.org/content/medrxiv/early/2025/07/11/2025.07.10.25331321.full.pdf
- OA Status
- green
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4412354954
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4412354954Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.1101/2025.07.10.25331321Digital Object Identifier
- Title
-
Genome-wide insights into generalised anxiety using a dimensional symptom severity approachWork title
- Type
-
preprintOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2025Year of publication
- Publication date
-
2025-07-11Full publication date if available
- Authors
-
Megan Skelton, Brittany L. Mitchell, Elham Assary, Danyang Li, Geneviève Morneau‐Vaillancourt, Alan E Murphy, Abigail ter Kuile, Ying Wang, Mark J. Adams, Enda M. Byrne, Elizabeth C. Corfield, P Grimes, Laurie J. Hannigan, Jihua Hu, Kadri Kõiv, Alex S. F. Kwong, Sergi Papiol, Johanne Hagen Pettersen, Giorgio Pistis, Enrique Castelao, Nora I. Strom, Peter J. van der Most, Ole A. Andreassen, Angelika Erhardt, Alexandra Havdahl, Nathan Skene, Brad Verhulst, Heike Weber, Chérie Armour, Helga Ask, William 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 Walters, Naomi R. Wray, Catharina A. Hartman, Nicholas G. Martin, John M. Hettema, Gerome Breen, Jonathan R. I. Coleman, Thalia C. EleyList of authors in order
- Landing page
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https://doi.org/10.1101/2025.07.10.25331321Publisher landing page
- PDF URL
-
https://www.medrxiv.org/content/medrxiv/early/2025/07/11/2025.07.10.25331321.full.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
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https://www.medrxiv.org/content/medrxiv/early/2025/07/11/2025.07.10.25331321.full.pdfDirect OA link when available
- Concepts
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Anxiety, Neuroticism, Genome-wide association study, Heritability, Depression (economics), Irritable bowel syndrome, SNP, Clinical psychology, Genetic association, Medicine, Psychiatry, Psychology, Genetics, Gene, Single-nucleotide polymorphism, Biology, Personality, Genotype, Macroeconomics, Economics, Social psychologyTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
0Total citation count in OpenAlex
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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