Anxiety in the genome: New genetic links to anxiety symptoms

Anxiety is a vital warning system in humans. Yet for millions of people affected, this function becomes unbalanced and develops into a debilitating condition. A new international study involving nearly 700,000 participants, published in *Nature Human Behaviour*, now provides the most comprehensive evidence to date on the genetic basis of anxiety – and thus takes a major step forward in a research goal that has spanned decades.

Anxiety, fear and worry are normal stress responses that help us to stay alert and react cautiously in potentially dangerous situations. For an increasing number of people, however, these symptoms become more intense. They develop an anxiety disorder, which can lead to problems in everyday life and significant distress. Anxiety disorders are among the most common mental health conditions worldwide. To better understand the biological architecture of anxiety, the Anxiety Working Group was established as part of the international research initiative PGC (Psychiatric Genomics Consortium). Jürgen Deckert, a psychiatrist and anxiety researcher from Würzburg, played a leading role in establishing this working group.

The PGC Anxiety working group, in collaboration with Würzburg University Hospital and other members of the TRR 58 Collaborative Research Centre ‘Fear, Anxiety and Anxiety Disorders’ – which was funded by the DFG between 2008 and 2020 – has now published new insights into the genetic mechanisms of anxiety disorders in the specialist journal *Nature Human Behaviour*.

What genetic differences do those affected commonly exhibit?

The so-called genome-wide association study (GWAS) was led by Thalia Eley at King’s College London and the QIMR Berghofer Medical Research Institute. In Würzburg, alongside Jürgen Deckert, Nora Strom, Angelika Erhardt-Lehmann (co-chair of the PGC Anxiety Working Group) and Heike Weber also worked on this study, the world’s largest analysis of DNA in relation to anxiety disorders. In the genetic analysis of 693,869 people of European descent, the study team identified the largest number of genetic associations with anxiety to date. “By linking the genetic data in our study not only to a clinical ‘yes’ or ‘no’ diagnosis, but also to the severity of symptoms, we gained a new understanding of anxiety as a biological continuum – ranging from normal stress responses to severely debilitating disorders,” says Jürgen Deckert, explaining what makes the study unique.

74 genetic links to anxiety

In total, the study identified 74 loci in the genome where genetic variations were associated with anxiety symptoms. Around half of these were already known from earlier GWAS studies on anxiety, such as the GWAS study published this year in *Nature Genetics* with Nora Strom as the first author. However, 39 loci were described for the first time.

In addition to this large number of new genetic markers, the results also show that certain genes may play a role in anxiety, for example PCLO and SORCS3. Many of the genes involved are particularly active in the brain and play a part in how nerve cells communicate with one another.

Furthermore, the analysis showed that known genetic differences account for only around 6 per cent of the variation in the severity of anxiety symptoms between different people. The majority of genetic influences therefore remain unknown.

Genetics is only part of the risk – rising anxiety rates point to environmental factors

Megan Skelton, a research fellow at the IoPPN at King’s College London, believes the study represents an exciting step forward in understanding how the risk of anxiety can be influenced by biological processes. However, the study’s lead author is keen to emphasise that even someone with a very high genetic risk does not necessarily develop an anxiety disorder, and conversely, someone with a low genetic risk may well develop one: “Genetic influences act in conjunction with life experiences, social contexts and psychological factors, and interact with them to shape an individual’s risk. The rise in anxiety rates that we are observing points to environmental factors. Understanding genetic risks can help us identify who might be particularly vulnerable to these factors and ultimately contribute to more effective prevention and treatment strategies.”

Polygenic risk scores

The study also calculated polygenic risk scores (PRS) for anxiety, which summarise each individual’s genetic risk in a single number. These were based on the results of a genome-wide association study (GWAS) of people of European descent. The scores were then tested in separate groups of people of European, African and South Asian descent. The genetic risk scores explained only a small proportion (1.2 to 2.9 per cent) of the differences in the severity of anxiety symptoms between individuals. The results suggest that there are, to some extent, shared genetic influences across different ethnic population groups. Further studies across different ethnic groups are needed to better understand specific genetic risks.

Mental and physical health are closely linked

A broad spectrum of significant genetic correlations was also observed between anxiety and both mental and physical illnesses, including depression, irritable bowel syndrome, chronic pain, coronary heart disease, endometriosis and migraine.

“These correlations highlight the interrelationship between mental and physical health,” says Brittany Mitchell, head of the ‘Complex Trait Genomics’ research group at the QIMR Berghofer Medical Research Institute and co-first author of the study. “Importantly, some shared genetic variants can increase the risk of both a physical illness and more severe anxiety symptoms. At the same time, living with chronic pain or a chronic illness can itself contribute to anxiety symptoms. Our findings do not establish causality or the direction of causation, but they do raise important questions for future research.”

Summary and outlook

Thalia Eley, Professor of Developmental and Behavioural Genetics at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and lead author of the study, summarises: “Despite the impact of anxiety disorders on public health, progress in understanding their genetic basis lags behind that of other major mental health conditions. Given the high and rising rates of anxiety, particularly among young adults, it is more important than ever to improve our ability to identify and understand risk factors. We hope that our findings will spur a new wave of large-scale analyses to accelerate our understanding of the genetic architecture of anxiety.” Jürgen Deckert adds: “The Psychiatric Genomic Consortium for Anxiety will continue to pursue its mission with great dedication, building on these initial groundbreaking findings, ultimately with the aim of developing innovative and personalised therapies for those affected.”

Original publication

Skelton, M., Mitchell, B.L., Assary, E. et al. Genome-wide meta-analysis of quantitatively measured generalised anxiety symptoms in individuals of European ancestry. Nat Hum Behav (2026). https://doi.org/10.1038/s41562-026-02476-7