Genome-wide insights into generalised anxiety using a dimensional symptom severity approach

Skelton M, Megan Skelton, Mitchell BL, Brittany L Mitchell, Assary E, Elham Assary, Li D, Danyang Li, Morneau-Vaillancourt G, Genevieve Morneau-Vaillancourt, Alan E Murphy, Murphy AE, ter Kuile AR, Abigail R Ter Kuile, Rujia Wang, Wang R, Adams MJ, Mark J Adams, Byrne EM, Enda M. Byrne, Corfield EC, Elizabeth C Corfield, Grimes PZ, Poppy Z Grimes, Laurie J Hannigan, Hannigan LJ, Jihua Hu, Hu J, Koiv K, Kadri Koiv, Kwong AS, Alex Sf Kwong, Papiol S, Sergi Papiol, Johanne H Pettersen, Pettersen JH, Pistis G, Giorgio Pistis, Enrique Castelao, Castelao E, Strom NI, Nora I Strom, Peter J van der Most, van der Most PJ, Anxiety Disorders Working Group of the Psychiatric Genomics Consortium, GLAD+ authors, Lifelines Cohort Study, NIHR Bioresource, PROTECT-AD Consortium, Andreassen OA, Ole A Andreassen, Angelika Erhardt-Lehmann, Erhardt-Lehmann A, Havdahl A, Alexandra Havdahl, Nathan Skene, Skene N, Brad Verhulst, Verhulst B, Heike Weber, Weber H, Cherie Armour, Armour C, Helga Ask, Ask H, William E Copeland, Copeland WE, Udo Dannlowski, Dannlowski U, Jurgen Deckert, Deckert J, Katharina Domschke, Domschke K, Ian B Hickie, Hickie IB, Lehto K, Kelli Lehto, Lonsdorf TB, Tina B Lonsdorf, Ulrike Lueken, Lueken U, Michelle K Lupton, Lupton MK, Medland SE, Sarah E. Medland, Andrew M McIntosh, McIntosh AM, Oldehinkel AJ, Albertine J Oldehinkel, Preisig M, Martin Preisig, Reif A, Andreas Reif, Snieder H, Harold Snieder, James T R Walters, Walters JT, Wray NR, Naomi R. Wray, Hartman CA, Catharina A Hartman, Nicholas G. Martin, Martin NG, Hettema JM, John M Hettema, Breen G, Gerome Breen, Coleman JR, Jonathan Ri Coleman, Eley TC, Thalia C Eley
other preprint OA: green public-domain-us
AI-generated summary by gemini-2.5-flash-lite, 2026-06-11

This genome-wide meta-analysis of generalized anxiety symptom severity identified 82 variants in 76 loci, implicated synaptic and axonal processes, and found significant genetic correlations with multiple mental and physical health traits.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

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.

My notes (saved in your browser only)

Ask this paper AI returns verbatim quotes from the full text · source: pmc

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosisirritable_bowel_syndrome

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2025) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

crossref
last seen: 2026-08-15T06:29:43.268988+00:00
europepmc
last seen: 2026-08-17T06:23:50.590068+00:00
pmc
last seen: 2026-05-13T20:22:03.195721+00:00
pubmed
last seen: 2026-08-17T06:07:51.610703+00:00
unpaywall
last seen: 2026-05-11T08:34:28.763810+00:00
License: public-domain-us · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine