Anxiety disorders — including generalized anxiety disorder, panic disorder and phobias — affect as many as one in four people over the course of their lives. They often begin early in life and persist for years, inflicting significant personal, social and economic consequences.
Now, a major breakthrough published in Nature Genetics is offering the clearest picture yet of the genetic roots of these conditions.
In what is now the largest genome‑wide association study (GWAS) of clinically diagnosed anxiety disorders ever conducted, an international team led by researchers from Texas A&M University, Dalhousie University, King's College London and Würzburg JMU University analyzed genetic data from 122,341 people diagnosed with major anxiety disorders and 729,881 controls.
The researchers identified 58 independent genetic variants associated with increased anxiety risk that pointed to 66 genes that appear to influence how our brain responds to stress and threat.
"Anxiety disorders and their underlying sources of genetic risk have been understudied compared to other psychiatric conditions, so this study substantially advances this critical knowledge," said the study's senior author, Dr. Jack Hettema , professor from the Department of Psychiatry and Behavioral Sciences at the Texas A&M University Naresh K. Vashisht College of Medicine . "Anxiety disorders have long been recognized as heritable, but until now we lacked a solid link between anxiety and the specific genetic factors involved."
The genetic roots of anxiety disorders are complex
Rather than being driven by a single "anxiety gene," the findings emphasize that anxiety disorders are influenced by a large number of genetic variants from across the genome, with each variant that a person inherits subtly changing an individual's genetic risk for developing anxiety-related conditions. This is consistent with the genetic architecture for common medical conditions like hypertension and clinical depression.
The researchers found strong genetic overlap between anxiety disorders and related traits including depression, neuroticism, PTSD and suicide attempts, reinforcing decades of clinical observations.
"Anxiety rarely occurs in isolation," said study co-author Dr. Brad Verhulst , research assistant professor in the Department of Psychiatry and Behavioral Sciences, the Naresh K. Vashisht College of Medicine. "Our findings help explain their frequent co‑occurrence, underscoring the shared biology behind these forms of emotional distress."
Key brain‑calming system emerges as central to anxiety biology
Notably, the study highlighted genes involved in GABAergic signaling, a key system that regulates brain activity. GABA (gamma-aminobutyric acid) is already targeted by several existing anti-anxiety medications, providing converging evidence for brain circuits and biochemical systems that have long been suspected to be involved in anxiety.
GABA is a natural chemical found in the brain that helps calm activity in the nervous system, telling overactive nerve cells to "slow down." Hettema emphasizes: "Our genomic findings provide converging evidence of the central role GABA plays for a part of the basis for clinical anxiety."
Genes influence risk, but environment and experience still matter
Verhulst stressed that genes alone don't seal a person's fate. "Our discoveries highlight underlying biological vulnerability for anxiety, but they don't diminish the profound influence of lived experience," he said. "Clarifying the influence of genetic factors that increase the risk of experiencing clinical anxiety may, in the future, help us to identify people who are particularly vulnerable. Our findings provide a starting point for developing early‑intervention strategies and more effective, personalized treatments."
Discoveries pave the way for future treatments and personalized care
The authors say the newly identified variants and implicated pathways provide a roadmap for future research.
"By prioritizing genes for follow‑up studies, scientists can begin to explore the molecular pathways that influence anxiety risk over time," Hettema said. "The insights also lay the groundwork for a more nuanced understanding of the biology of anxiety that, in the future, may improve diagnostic clarity and, eventually, targeted therapeutics."
Nevertheless, Hettema stressed that the results do not support the use of genetic testing to diagnose anxiety. "Identifying specific genes and biological pathways that contribute to mental health problems may help scientists better understand how anxiety develops," he said, "and could inform the future development of new treatments or the improvement of existing ones."
By Lesley Henton, Texas A&M University Division of Marketing and Communications
