Strom, Nora I;
Verhulst, Brad;
Bacanu, Silviu-Alin;
Cheesman, Rosa;
Purves, Kirstin L;
Gedik, Hüseyin;
Mitchell, Brittany L;
... Hettema, John M; + view all
(2026)
Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.
Nature Genetics
10.1038/s41588-025-02485-8.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41588-025-02485-8 |
| Publisher version: | https://doi.org/10.1038/s41588-025-02485-8 |
| Language: | English |
| Additional information: | This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Division of Psychiatry |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10221033 |
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