Anxiety is faced by 58 genetic variants, not single gene, says study

Researchers have found 58 genetic variants linked to an increased risk of anxiety, suggesting that the disorder is not driven by a “single anxiety gene”.

The researchers, led by those from Texas A&M University in the U.S., said that anxiety disorders are influenced by genetic variants from across the human genome, with each variant inherited subtly changing an individual’s genetic risk for developing anxiety-related conditions.

The findings are consistent with the genetic architecture for common medical conditions like hypertension and clinical depression, they said.

The 58 genetic variants analysed in the study, published in the journal Nature Genetics, pointed to 66 genes that the researchers said appear to influence how the brain responds to stress and threat.

The team also found a strong genetic overlap between anxiety disorders and related traits including depression, neuroticism, post traumatic stress disorder (PTSD) and suicide attempts — the results reinforced decades of clinical observations, they said.

“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,” senior author Jack Hettema, professor from the department of psychiatry and behavioral sciences at the Texas A&M University, said.

“Anxiety disorders have long been recognised as heritable, but until now we lacked a solid link between anxiety and the specific genetic factors involved,” Hettema said.

The researchers analysed genetic data from 122,341 people diagnosed with major anxiety disorders and 729,881 without.

The authors “identified 58 independent genome-wide significant risk variants and 66 genes with robust biological support.” They also found a “substantial genetic correlation between (anxiety) and depression, neuroticism and other internalising phenotypes.” The analysis highlighted genes involved in the regulation of the ‘GABA’ brain chemical as a potential mechanism critical in one’s genetic risk of anxiety — GABA helps calm down activity in the nervous system.

GABA, or gamma-aminobutyric acid, is already targeted by several existing anti-anxiety medications, and thus, the study provides converging evidence for brain circuits and biochemical systems long suspected to be involved in anxiety, the researchers said.

They added that genes alone do not seal a person’s fate.

“Our discoveries highlight underlying biological vulnerability for anxiety, but they don’t diminish the profound influence of lived experience,” co-author Brad Verhulst, research assistant professor in the department of psychiatry and behavioral sciences at the Texas A&M University, 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, personalised treatments,” Verhulst said.

The authors said the newly identified variants and implicated pathways provide a roadmap for future research.