Summary: A major genome-wide association study (GWAS) on anxiety has revealed the complex polygenic architecture underlying worry and fear-related responses by analysing genomic data from 693,869 individuals. This large meta-analysis shifts psychiatric genetics toward measuring continuous symptom severity rather than relying solely on binary clinical diagnoses, offering new biological insights and potential targets for early screening and tailored treatment.
An international team identified 74 distinct genomic loci associated with anxiety symptom severity, including 39 novel regions. Many implicated genes are highly expressed in brain tissue and play roles in synaptic and axonal processes that regulate neuronal communication, highlighting biological mechanisms that influence individual vulnerability to anxiety.
Key Facts
- Measuring a Biological Continuum: Researchers assessed quantitative anxiety symptom severity across nearly 700,000 people, treating anxiety as a spectrum that ranges from adaptive vigilance to clinically significant disorder.
- Seventy-four Genetic Loci: The analysis detected 80 independent genome-wide significant variants within 74 loci; 39 of these loci are newly associated with anxiety, expanding the catalogue of genetic risk factors.
- Brain and Synaptic Biology: Several implicated genes, including PCLO and SORCS3, are enriched in brain tissue and involved in synaptic transmission and neuronal signaling, suggesting anxiety risk is linked to variation in neural communication and wiring.
- Heritability and Explained Variance: Common genetic variation accounts for approximately 6% of individual differences in anxiety symptom severity, leaving substantial influence from environmental exposures, life experiences, and complex gene–environment interplay.
- Rising Anxiety and the Environment: Because genetic change across generations is minimal, increasing anxiety prevalence—notably among young adults—likely reflects social and environmental shifts rather than altered population genetics.
- Polygenic Scores and Ancestry Gaps: Polygenic risk scores derived from European-ancestry GWAS explained 1.2%–2.9% of variance in anxiety severity across European, African and South Asian samples. These results point to shared genetic foundations but underscore the urgent need for more diverse biobank data, particularly from African and South Asian populations, to build accurate population-specific risk models.
- Mental–Physical Health Overlap: The study found genetic correlations between anxiety and a range of physical and psychiatric conditions, including depression, irritable bowel syndrome (IBS), chronic pain, coronary artery disease, endometriosis and migraine, highlighting interconnected biological pathways.
Source: King’s College London
A collaborative team led by scientists at King’s College London and QIMR Berghofer Medical Research Institute analysed genetic data on anxiety symptoms in 693,869 people of European ancestry. Published in Nature Human Behaviour, the study represents the largest GWAS to date focused on anxiety symptom severity and demonstrates the advantage of analysing quantitative traits rather than binary case–control definitions in psychiatric genetics.
Anxiety disorders are the most common mental health conditions worldwide, and reported rates have been rising. Symptoms vary widely across the population, reflecting the evolutionary role that fear and worry play in promoting vigilance and responding to threats. By studying symptom severity across a broad population, the research captures this variability and reveals genetic contributions to the full spectrum of anxiety.
Professor Thalia Eley, lead author and Professor of Developmental Behavioural Genetics at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London, emphasised the importance of large-scale, symptom-focused analyses to accelerate understanding of anxiety genetics and to improve the identification of sources of risk.
Dr Megan Skelton, first author and Research Fellow at IoPPN, noted that genetic risk interacts with life experiences, social context and psychological factors. Genetic predisposition does not determine outcome: people with higher genetic risk may remain well if environmental exposures are limited, while others with lower genetic risk can develop significant anxiety in adverse contexts. Understanding genetic sensitivity can help target prevention and treatment strategies to those most vulnerable.
Co-first author Dr Brittany Mitchell from QIMR Berghofer highlighted that the observed genetic correlations with physical health conditions underscore the complex relationship between mental and physical health. Shared genetic variants may contribute to both anxiety and certain physical illnesses, while living with chronic health problems can also increase anxiety symptoms. These associations do not establish causation but point to avenues for future research.
Funding: This work was an output of the Psychiatric Genomics Consortium and received partial funding from the US National Institutes of Health (NIH). Additional support came from bodies including the Wellcome Trust, the UK Medical Research Council (MRC), the NIHR Maudsley Biomedical Research Centre and the Australian National Health and Medical Research Council.
Key Questions Answered:
A: Measuring symptom severity treats anxiety as a continuous trait, capturing subtle differences across the population. This approach increases statistical power to detect genetic influences and better reflects the biological continuum from normal stress responses to clinical disorder.
A: The study implicates genes that regulate synaptic and axonal processes, indicating that variations in neuronal communication and circuit function contribute to anxiety risk. Genes such as PCLO and SORCS3 are among those highlighted for their roles in brain signaling.
A: Environmental and societal factors are the primary drivers of rising anxiety prevalence. Because population genetics remain relatively stable across generations, increased exposure to stressors, social changes and other environmental influences likely account for the observed rise.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by 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 and colleagues. Published in 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 responses to clinical disorder. This genome-wide association meta-analysis included 693,869 individuals of European ancestry from 14 cohorts and identified 80 independent genome-wide significant variants within 74 loci, 39 of which were newly associated with anxiety. SNP-based heritability was estimated at 5.9%. Polygenic scores were significantly associated with anxiety symptom severity and disorder across European, African and South Asian ancestry samples (R2 = 1.2–2.9%).
Significant genetic correlations were observed 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 demonstrate the discovery power gained from analysing a quantitative trait rather than a case–control phenotype in anxiety genetics.