“Richest Set of Results to Date” Pinpoint Six Genes That Are Linked to Anxiety Disorders

A new collaborative research study of over 200,000 military veterans has discovered six genetic variants that are linked to anxiety.

According to statistics from the Anxiety and Depression Association of America, anxiety disorders are the most common mental illnesses in the U.S., affecting a staggering 18.1% of the population each year.

Suffering from an anxiety disorder can have major adverse effects on an individual's quality of life; it may prevent them from being able to socialize, to work, or to engage in relationships, for example. Individuals with an anxiety disorder are three to five times more likely to go to the doctor, and six times more likely to be hospitalized when compared to those who do not suffer from an anxiety disorder.

Anxiety disorders – like all psychiatric conditions – are complex in their pathophysiology. We don't know exactly what causes them, and therefore, our knowledge on how to treat them is somewhat incomplete. A variety of pharmacological and non-pharmacological treatment options are available; however, they are often limited in success and may only benefit certain individuals.

Exploring the role of genetics in anxiety disorders

A number of factors may contribute to an individual's likelihood of developing an anxiety disorder, including lifestyle choices and experiences, and genetics.

An increasing amount of research is focusing on the contribution of genetics to the development of mental health conditions. Murray Stein, San Diego VA staff psychiatrist and Distinguished Professor of Psychiatry and of family medicine and public health at UCSD points out "While there have been many studies on the genetic basis of depression, far fewer have looked for variants linked to anxiety, disorders of which afflict as many as one in ten Americans."

Stein is the senior author of a new study, published in the American Journal of Psychiatry , that explores the contribution of certain genetic variants to the development of anxiety disorders.  

The research, a genome wide association study (GWAS), analyzed the genomes of approximately 200,000 military veterans from the Million Veteran Program (MVP). From the data, they discovered six genetic variants linked to anxiety. Five were identified in European Americans and one was identified in African Americans.

A selection of these variants has also been previously linked to other conditions such as bipolar disorder, schizophrenia and posttraumatic stress disorder.

"This is the richest set of results for the genetic basis of anxiety to date," said co-lead author Joel Gelernter, the Foundations Fund Professor of Psychiatry, professor of genetics and of neuroscience at Yale. "There has been no explanation for the comorbidity of anxiety and depression and other mental health disorders, but here we have found specific, shared genetic risks."

More about the MVP

The MVP is a national research program that was implemented in 2011 and currently has over 775,000 veteran recruits. Its primary goal is to explore how genetics, lifestyle factors and military exposure can ultimately impact an individual's health.

The MVP offers the opportunity to study a large data set that would otherwise be difficult to gather and collate. Thus far, several studies have utilized the MVP data to make interesting discoveries relating to genetics and psychiatric disorders. Gelernter says, "This is a rich vein we have just begun to tap."

A role for sex hormones?

Of the six variants identified, MAD1L1, a gene which (to date) has not been fully characterized, was "highly notable" and is linked to a variety of other psychiatric illnesses.

Also of note is the fact that some of the genetic variants identified were linked to genes that regulate hormonal activity, specifically in relation to the sex hormone estrogen. As more females are affected by an anxiety disorder than males, this is an intriguing finding. However, the scientists emphasize that the research sample from the MVP largely consists of men, which could be considered a study limitation.

Nonetheless, the research serves as a contributor to the pool of research expanding our knowledge of the molecular underpinnings of psychiatric disorders.

"One of the goals of this research is to find important risk genes that are associated with risk for many psychiatric and behavioral traits for which we don't have a good explanation," Yale's Daniel Levey, a postdoctoral associate and co-lead author of the study, concludes.  

Reference: Levey et al. (2020). Reproducible Genetic Risk Loci for Anxiety: Results from ~200,000 Million Veteran Program Participants. The American Journal of Psychiatry. DOI:  https://doi.org/10.1101/540245.