TY - JOUR
T1 - Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling
AU - Veterans Affairs Million Veteran Program
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AU - 23andMe Research Team
AU - Strom, Nora I.
AU - Verhulst, Brad
AU - Bacanu, Silviu Alin
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AU - Gedik, Hüseyin
AU - Mitchell, Brittany L.
AU - Kwong, Alex S.
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AU - Ströhle, Andreas
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AU - Breen, Gerome
AU - Docherty, Anna R.
AU - Coon, Hilary
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AU - Mattheisen, Manuel
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N1 - Publisher Copyright:
© The Author(s) 2026.
PY - 2026/2
Y1 - 2026/2
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105029474297
U2 - 10.1038/s41588-025-02485-8
DO - 10.1038/s41588-025-02485-8
M3 - Article
C2 - 41634414
AN - SCOPUS:105029474297
SN - 1061-4036
VL - 58
SP - 275
EP - 288
JO - Nature genetics
JF - Nature genetics
IS - 2
ER -