Summary: The largest genome-wide association study (GWAS) on anxiety to date has mapped the complex polygenic architecture underlying worry and fear-based responses. The massive meta-analysis evaluated genomic data from 693,869 individuals. The study marks a paradigm shift in psychiatric genetics by tracking the continuous spectrum of symptom severity rather than relying on a binary clinical diagnosis.
The international team successfully pinpointed 74 distinct genomic locations associated with anxiety, including 39 entirely novel discoveries. Many of these genes operate directly within brain tissue to regulate neural transmission, offering fresh biological targets to guide early screening and specialized clinical therapeutics.
Key Facts
- Shifting to a Biological Continuum: Instead of using rigid “yes or no” clinical diagnoses, researchers analyzed the specific severity of anxiety symptoms across nearly 700,000 individuals. This approach acknowledges anxiety as a continuous biological spectrum ranging from normal, evolutionary threat vigilance to severe, debilitating disorders.
- Unmasking 74 Genome Locations: The study uncovered the largest collection of anxiety-associated genetic loci to date. Out of the 74 identified genomic regions, 39 are entirely novel discoveries, substantially expanding our map of genetic risk factors.
- Brain Tissue & Synaptic Communication: The identified genes, including PCLO and SORCS3, are highly active in brain tissue. They primarily control how nerve cells communicate with one another, suggesting that individual differences in synaptic transmission directly influence anxiety vulnerability.
- The 6% Common Genetic Baseline: Common genetic variations explain roughly 6% of the differences in anxiety severity between people. This leaves the remaining variance driven by environmental stressors, life experiences, and complex gene-environment interactions.
- The Environmental Rise Paradox: Because human genetics do not change across single generations, researchers emphasize that rising global anxiety rates, particularly among young adults—are driven by environmental and societal factors, rather than a shifting genetic blueprint.
- Polygenic Score Ancestry Gaps: Using European-ancestry data, the team calculated polygenic risk scores that explained 1.2% to 2.9% of anxiety variance across diverse populations. While this confirms shared genetic foundations, the authors stress an urgent need for biobanks to collect more data from African and South Asian ancestries to build accurate, population-specific risk models.
- The Mental-Physical Health Intersection: The analysis revealed broad genetic overlaps between anxiety and several chronic physical conditions, including depression, irritable bowel syndrome (IBS), chronic pain, coronary artery disease, endometriosis, and migraines.
Source: King’s College London
A study led by researchers at King’s College London and QIMR Berghofer medical research institute analysed genetic data on anxiety symptoms in 693,869 people of European ancestry, revealing new insight into the genetic pathways involved in the condition.
Published in Nature Human Behaviour, the research has found the largest number of genetic associations with anxiety to date. By linking genetic data to severity of symptoms rather than the yes/no category of a clinical diagnosis, it brings new understanding to the biological continuum behind anxiety that can range from healthy stress responses to debilitating disorder.
Anxiety disorders are the most prevalent mental health conditions worldwide and rates are rising. Symptoms vary in their intensity and type throughout the population, reflecting the evolutionary function that fear and worry serve by enabling vigilance and caution in response to potential threats.
The new research is a genome wide association study (GWAS) and analyses the DNA of many people – in this case nearly 700,000 – to identify which genetic differences occur more often in those who experience more severe anxiety symptoms.
Professor Thalia Eley, Professor of Developmental Behavioural Genetics at Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London and lead author on the study said: “Despite the public health impact of anxiety, progress in the understanding of its genetics lags behind other major mental health conditions. Given the high and rising rates of anxiety, especially in young adults, it is more important than ever to improve our ability to identify and understand sources of risk. We hope our findings encourage a new wave of large-scale analyses to accelerate our progress in understanding the genetic architecture of anxiety.”
The study identified 74 locations in the genome where genetic differences were linked to anxiety symptoms. Around half of these have been reported in previous anxiety GWAS, but the remainder (39 of the loci) were novel.
Beyond identifying the largest number of anxiety-associated loci to date, the results provide support for the role of certain genes in anxiety, such as PCLO and SORCS3. Many of the implicated genes are particularly active in brain tissue and are involved in how nerve cells communicate with each other.
The analysis also found that common genetic variation explains around 6% of the differences in anxiety symptom severity between people, leaving substantial room for environmental influences, gene-environment interactions, and undetected genetic effects.
Dr Megan Skelton, Research Fellow at IoPPN, King’s College London and first author on the study said: “This is an exciting step forward in understanding how anxiety risk can be influenced by biological processes. It’s important to highlight that genetics interplay with life experiences, social contexts, and psychological factors to shape individual risk.
“This means that even someone with a high genetic risk might not develop anxiety, while someone with low genetic risk could. The rise in anxiety rates points to environmental factors, as genetics don’t change much across generations, so reducing anxiety in the population will require these factors to be addressed.
“At the same time, understanding genetic risk could help us identify people who are more sensitive to environmental influences, ultimately contributing to more effective prevention and treatment strategies.”
The researchers also calculated polygenic scores for anxiety, which summarise each individual’s genetic risk. The scores were created using the European-ancestry GWAS results, in separate samples of people from European, African and South Asian populations, and explained 1.2% to 2.9% of the variance in anxiety symptom severity.
The polygenic risk score results provide some support for shared genetic influences across these groups, but ancestry-specific GWAS remain necessary to identify population-specific genetic risk. At present, there are not enough datasets available with information on both anxiety symptoms and genetics in people with African or South Asian ancestry to run statistically meaningful GWAS.
There was a broad range of significant genetic correlations of anxiety with both mental and physical health conditions, including depression, irritable bowel syndrome, chronic pain, coronary artery disease, endometriosis and migraine.
Dr Brittany Mitchell, Team Head of The Complex Trait Genomics group at the QIMR Berghofer medical research institute and co-first author on the study said: “These correlations highlight the interconnection between mental and physical health.
“Importantly, while some shared genetic variants may increase risk for both a physical health condition and more severe anxiety symptoms, it’s also true that living with chronic pain or illness can contribute to anxiety symptoms. Our findings don’t reveal causation or the direction of effect, but they do open up important questions for future research.”
Funding: The study was an output of the Psychiatric Genomics Consortium, which is a group of scientists that focus on meta- and mega-analyses of psychiatric genetic studies. This phase of work by the Consortium was partially funded by the US National Institute for Health (NIH).
The researchers were supported by a range of bodies including the Wellcome Trust, the Medical Research Council (MRC), the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and the Australian National Health and Medical Research Council.
Key Questions Answered:
A: Because it views anxiety as a natural spectrum rather than a simple switch. Traditional studies only compare people who have a formal diagnosis against those who don’t. By measuring the fluid severity of symptoms across nearly 700,000 people, this study maps the true biological continuum of anxiety, from healthy everyday stress responses to severe disorders.
A: It pointed directly to cellular communication lines. The study isolated 74 genetic locations tied to anxiety, and many of these genes, such as PCLO and SORCS3, are heavily active in brain tissue. They dictate how nerve cells pass signals back and forth across synapses, showing that anxiety risk is deeply tied to variations in brain wiring.
A: Environmental and social factors are driving the surge. Because a population’s genetic blueprint cannot change over a few short generations, the rising rates point squarely to modern environmental stressors. Identifying genetic risk profiles helps scientists understand who is most vulnerable to these external pressures, but reducing population-wide anxiety requires addressing the environmental triggers.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by our staff.
About this genetics and anxiety research news
Author: Franca Davenport
Source: King’s College London
Contact: Franca Davenport – King’s College London
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Genome-wide analyses of quantitative generalised anxiety symptom severity” by Megan Skelton, Brittany L. Mitchell, Elham Assary, Danyang Li, Genevieve Morneau-Vaillancourt, Alan E. Murphy, Abigail R. ter Kuile, Rujia Wang, Mark J. Adams, Enda M. Byrne, Elizabeth C. Corfield, Poppy Z. Grimes, Laurie J. Hannigan, Jihua Hu, Kadri Kõiv, Alex S. F. Kwong, Sergi Papiol, Johanne H. Pettersen, Giorgio Pistis, Enrique Castelao, Nora I. Strom, Peter J. van der Most, Anxiety Disorders Working Group of the Psychiatric Genomics Consortium, GLAD+ authors, Lifelines Cohort Study, NIHR BioResource, PROTECT-AD Consortium, Ole A. Andreassen, Angelika Erhardt-Lehmann, Alexandra Havdahl, Nathan Skene, Brad Verhulst, Heike Weber, Chérie Armour, Helga Ask, William E. Copeland, Udo Dannlowski, Jürgen Deckert, Katharina Domschke, Ian B. Hickie, Kelli Lehto, Tina B. Lonsdorf, Ulrike Lueken, Michelle K. Lupton, Sarah E. Medland, Andrew M. McIntosh, Albertine J. Oldehinkel, Martin Preisig, Andreas Reif, Harold Snieder, James T. R. Walters, Naomi R. Wray, Catharina A. Hartman, Nicholas G. Martin, John M. Hettema, Gerome Breen, Jonathan R. I. Coleman & Thalia C. Eley. Nature Human Behaviour
DOI:10.1038/s41562-026-02476-7
Abstract
Genome-wide analyses of quantitative generalised anxiety symptom severity
Anxiety is heritable and exists on a continuum, with symptoms ranging from adaptive threat response to clinical disorder. Here we performed a genome-wide association meta-analysis of generalized anxiety symptom severity in 693,869 individuals of European ancestry from 14 cohorts.
We identified 80 independent genome-wide significant variants within 74 loci, 39 of which were newly associated with anxiety. SNP-based heritability was 5.9% (posterior s.d. = 0.15%). Polygenic scores were significantly associated with anxiety symptom severity and disorder in European, African and South Asian ancestry samples (R2 = 1.2–2.9%).
Significant genetic correlations (rg) were estimated with mental and physical health traits, including case–control anxiety, neuroticism and depression (rg = 0.71–0.85), 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 discovery power gained from analysing a quantitative trait rather than a case–control phenotype in anxiety genetics.
