| Title: | Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling |
| Journal: | Nature Genetics |
| Published: | 3 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41634414/ |
| DOI: | https://doi.org/10.1038/s41588-025-02485-8 |
| URL: | https://www.nature.com/articles/s41588-025-02485-8.pdf |
Publication 18377
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Abstract
The major anxiety disorders (ANX; including generalized anxiety disorder, panic disorder and phobias) are highly prevalent, often onset early and cause substantial global disability. Although distinct in their clinical presentations, they probably represent differential expressions of a dysregulated threat-response system. Here, we present a genome-wide association meta-analysis comprising 122,341 European ancestry ANX cases and 729,881 controls. We identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support. In an independent sample of 1,175,012 self-report ANX cases and 1,956,379 controls, 51 out of the 58 associations replicated. As predicted by twin studies, we found substantial genetic correlation between ANX and depression, neuroticism and other internalizing phenotypes. Follow-up analyses demonstrated enrichment in all major brain regions and highlighted GABAergic signaling as one potential mechanism implicated in ANX genetic risk. These results advance our understanding of the genetic architecture of ANX and prioritize genes for functional follow-up studies.</p>
13 Keywords
- Adult
- Anxiety Disorders
- Case-Control Studies
- Female
- Genetic Predisposition to Disease
- Genome-Wide Association Study
- Humans
- Male
- Phenotype
- Polymorphism, Single Nucleotide
- Signal Transduction
- White People
- gamma-Aminobutyric Acid
134 Authors
- Nora I. Strom
- Brad Verhulst
- Silviu-Alin Bacanu
- Rosa Cheesman
- Kirstin L. Purves
- Hüseyin Gedik
- Brittany L. Mitchell
- Alex S. Kwong
- Annika B. Faucon
- Kritika Singh
- Sarah Medland
- Lucia Colodro-Conde
- Kristi Krebs
- Per Hoffmann
- Stefan Herms
- Jan Gehlen
- Stephan Ripke
- Swapnil Awasthi
- Teemu Palviainen
- Elisa M. Tasanko
- Roseann E. Peterson
- Daniel E. Adkins
- Andrey A. Shabalin
- Mark J. Adams
- Matthew H. Iveson
- Archie Campbell
- Laurent F. Thomas
- Bendik S. Winsvold
- Ole Kristian Drange
- Sigrid Børte
- Abigail R. ter Kuile
- Joonas Naamanka
- Tan-Hoang Nguyen
- Sandra M. Meier
- Elizabeth C. Corfield
- Laurie Hannigan
- Daniel F. Levey
- Darina Czamara
- Heike Weber
- Karmel W. Choi
- Giorgio Pistis
- Baptiste Couvy-Duchesne
- Sandra Van der Auwera
- Alexander Teumer
- Robert Karlsson
- Miguel Garcia-Argibay
- Donghyung Lee
- Rujia Wang
- Ottar Bjerkeset
- Eystein Stordal
- Julia Bäckman
- Giovanni A. Salum
- Clement C. Zai
- James L. Kennedy
- Gwyneth Zai
- Arun K. Tiwari
- Stefanie Heilmann-Heimbach
- Börge Schmidt
- Jaakko Kaprio
- Martin M. Kennedy
- Joseph Boden
- Alexandra Havdahl
- Christel M. Middeldorp
- Fabiana L. Lopes
- Nirmala Akula
- Francis J. McMahon
- Elisabeth B. Binder
- Lydia Fehm
- Andreas Ströhle
- Enrique Castelao
- Henning Tiemeier
- Dan J. Stein
- David Whiteman
- Catherine Olsen
- Zachary Fuller
- Xin Wang
- Naomi R. Wray
- Enda M. Byrne
- Glyn Lewis
- Nicholas J. Timpson
- Lea K. Davis
- Ian B. Hickie
- Nathan A. Gillespie
- Lili Milani
- Johannes Schumacher
- David P. Woldbye
- Andreas J. Forstner
- Markus M. Nöthen
- Iiris Hovatta
- John Horwood
- William E. Copeland
- Hermine H. Maes
- Andrew M. McIntosh
- Ole A. Andreassen
- John-Anker Zwart
- Ole Mors
- Anders D. Børglum
- Preben B. Mortensen
- Helga Ask
- Ted Reichborn-Kjennerud
- Jackob M. Najman
- Murray B. Stein
- Joel Gelernter
- Yuri Milaneschi
- Brenda W. Penninx
- Dorret I. Boomsma
- Eduard Maron
- Angelika Erhardt-Lehmann
- Christian Rück
- Tilo T. Kircher
- Christiane A. Melzig
- Georg W. Alpers
- Volker Arolt
- Katharina Domschke
- Jordan W. Smoller
- Martin Preisig
- Nicholas G. Martin
- Michelle K. Lupton
- Annemarie I. Luik
- Andreas Reif
- Hans J. Grabe
- Henrik Larsson
- Patrik K. Magnusson
- Albertine J. Oldehinkel
- Catharina A. Hartman
- Gerome Breen
- Anna R. Docherty
- Hilary Coon
- Rupert Conrad
- Kelli Lehto
- Jürgen Deckert
- Thalia C. Eley
- Manuel Mattheisen
- John M. Hettema
1 Application
| Application ID | Title |
|---|---|
| 16577 | Investigations of the genetic overlap between internalising psychiatric disorders and co-morbid physical health disorders. |
Enabling scientific discoveries that improve human health