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Scientific Frontline: Extended "At a Glance" Summary: Novel Genetic Links with Anxiety Symptoms
The Core Concept: A record-breaking genome-wide association study (GWAS) of nearly 700,000 individuals identified 74 regions of the genome linked to anxiety, establishing a biological continuum by mapping genetic variance directly to symptom severity rather than a binary diagnosis.
Key Distinction/Mechanism: By shifting the focus from a simple clinical presence of anxiety to a spectrum of symptom severity, the research identified 39 novel genetic loci. It revealed that specific genes governing neural communication—such as PCLO and SORCS3—account for approximately 6% of the differences in anxiety intensity between individuals.
Major Frameworks/Components:
- Genome-Wide Association Studies (GWAS): The foundational methodology used to analyze large-scale DNA samples, correlating specific genetic markers with the severity of phenotypic traits.
- Polygenic Risk Scoring: The calculation of individual genetic risk profiles, which currently explains a 1.2% to 2.9% variance in symptom severity and highlights the critical need for ancestry-specific genomic data beyond European populations.
- Gene-Environment Interaction: The biological model confirming that genetic predispositions intersect with environmental factors, psychological stressors, and social contexts to manifest clinical anxiety.
- Genetic Pleiotropy: The observation of shared genetic variants between anxiety and both psychiatric (depression) and somatic conditions (chronic pain, irritable bowel syndrome, coronary artery disease).
Branch of Science: Genomics, Behavioral Genetics, Neuroscience, and Psychiatry.
Future Application: The formulation of precise polygenic risk scores to identify individuals who are highly sensitive to environmental stressors, thereby guiding targeted early interventions and accelerating the development of localized treatments for diverse ancestral populations.
Why It Matters: Anxiety disorders are the most prevalent mental health conditions globally. Isolating their complex genetic architecture separates inherent biological vulnerabilities from environmental triggers, providing the empirical foundation necessary to advance personalized psychiatric care.
A study led by researchers at King’s College London and the QIMR Berghofer Medical Research Institute analyzed 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 the severity of symptoms rather than the yes-or-no category of a clinical diagnosis, it brings new understanding to the biological continuum behind anxiety that can range from healthy stress responses to a 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 analyzes 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.
"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," said Thalia Eley, professor of developmental behavioral genetics at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London and lead author of the study.
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 the IoPPN at King’s College London and first author of the study, said, "This is an exciting step forward in understanding how anxiety risk can be influenced by biological processes. It is important to highlight that genetics interplays 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 a low genetic risk could.
"The rise in anxiety rates points to environmental factors, as genetics do not 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 summarize 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 they 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 migraines.
Dr. Brittany Mitchell, team head of the Complex Trait Genomics Group at the QIMR Berghofer Medical Research Institute and co-first author of the study, said, "These correlations highlight the interconnection between mental and physical health. Importantly, while some shared genetic variants may increase the risk for both a physical health condition and more severe anxiety symptoms, it is also true that living with chronic pain or illness can contribute to anxiety symptoms. Our findings do not reveal causation or the direction of effect, but they do open up important questions for future research."
Published in journal: Nature Human Behaviour
Authors: 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, and Thalia C. Eley
Source/Credit: King’s College London
Edited by: Scientific Frontline
Reference Number: geno060926_01
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