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
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by gemini-2.5-flash-lite, 2026-06-11
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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.
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.
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- 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
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Courtesy of the U.S. National Library of Medicine