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Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.

Publication ,  Journal Article
Strom, NI; Verhulst, B; Bacanu, S-A; Cheesman, R; Purves, KL; Gedik, H; Mitchell, BL; Kwong, AS; Faucon, AB; Singh, K; Medland, S; Krebs, K ...
Published in: Nat Genet
February 2026

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.

Duke Scholars

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

February 2026

Volume

58

Issue

2

Start / End Page

275 / 288

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • White People
  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Strom, N. I., Verhulst, B., Bacanu, S.-A., Cheesman, R., Purves, K. L., Gedik, H., … Hettema, J. M. (2026). Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling. Nat Genet, 58(2), 275–288. https://doi.org/10.1038/s41588-025-02485-8
Strom, Nora I., Brad Verhulst, Silviu-Alin Bacanu, Rosa Cheesman, Kirstin L. Purves, Hüseyin Gedik, Brittany L. Mitchell, et al. “Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.Nat Genet 58, no. 2 (February 2026): 275–88. https://doi.org/10.1038/s41588-025-02485-8.
Strom NI, Verhulst B, Bacanu S-A, Cheesman R, Purves KL, Gedik H, et al. Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling. Nat Genet. 2026 Feb;58(2):275–88.
Strom, Nora I., et al. “Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling.Nat Genet, vol. 58, no. 2, Feb. 2026, pp. 275–88. Pubmed, doi:10.1038/s41588-025-02485-8.
Strom NI, Verhulst B, Bacanu S-A, Cheesman R, Purves KL, Gedik H, Mitchell BL, Kwong AS, Faucon AB, Singh K, Medland S, Colodro-Conde L, Krebs K, Hoffmann P, Herms S, Gehlen J, Ripke S, Awasthi S, Palviainen T, Tasanko EM, Peterson RE, Adkins DE, Shabalin AA, Adams MJ, Iveson MH, Campbell A, Thomas LF, Winsvold BS, Drange OK, Børte S, Ter Kuile AR, Naamanka J, Nguyen T-H, Meier SM, Corfield EC, Hannigan L, Levey DF, Czamara D, Weber H, Choi KW, Pistis G, Couvy-Duchesne B, Van der Auwera S, Teumer A, Karlsson R, Garcia-Argibay M, Lee D, Wang R, Bjerkeset O, Stordal E, Bäckman J, Salum GA, Zai CC, Kennedy JL, Zai G, Tiwari AK, Heilmann-Heimbach S, Schmidt B, Kaprio J, Kennedy MM, Boden J, Havdahl A, Middeldorp CM, Lopes FL, Akula N, McMahon FJ, Binder EB, Fehm L, Ströhle A, Castelao E, Tiemeier H, Stein DJ, Whiteman D, Olsen C, Fuller Z, Wang X, Wray NR, Byrne EM, Lewis G, Timpson NJ, Davis LK, Hickie IB, Gillespie NA, Milani L, Schumacher J, Woldbye DP, Forstner AJ, Nöthen MM, Hovatta I, Horwood J, Copeland WE, Maes HH, McIntosh AM, Andreassen OA, Zwart J-A, Mors O, Børglum AD, Mortensen PB, Ask H, Reichborn-Kjennerud T, Najman JM, Stein MB, Gelernter J, Milaneschi Y, Penninx BW, Boomsma DI, Maron E, Erhardt-Lehmann A, Rück C, Kircher TT, Melzig CA, Alpers GW, Arolt V, Domschke K, Smoller JW, Preisig M, Martin NG, Lupton MK, Luik AI, Reif A, Grabe HJ, Larsson H, Magnusson PK, Oldehinkel AJ, Hartman CA, Breen G, Docherty AR, Coon H, Conrad R, Lehto K, Veterans Affairs Million Veteran Program, FinnGen, 23andMe Research Team, Deckert J, Eley TC, Mattheisen M, Hettema JM. Genome-wide association study of major anxiety disorders in 122,341 European-ancestry cases identifies 58 loci and highlights GABAergic signaling. Nat Genet. 2026 Feb;58(2):275–288.

Published In

Nat Genet

DOI

EISSN

1546-1718

Publication Date

February 2026

Volume

58

Issue

2

Start / End Page

275 / 288

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • White People
  • Signal Transduction
  • Polymorphism, Single Nucleotide
  • Phenotype
  • Male
  • Humans
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
  • Female