CLOUD

Largest genetic study of anxiety to date reports findings

A massive genome-wide analysis of approximately 200,000 military veterans has identified six genetic variants linked to anxiety, researchers from Yale and colleagues at other institutions report Jan. 7 in the American Journal of Psychiatry.

The study used VA Million Veteran Program (MVP) data to identify regions on the human genome related to anxiety risk. The findings could lead to new understanding and treatment of the condition, which affects 1 in 10 Americans.

Some of the variants associated with anxiety had previously been implicated as risk factors for bipolar disorder, posttraumatic stress disorder, and schizophrenia.

According to Dr. Dan Levey of the VA Connecticut Healthcare Center and Yale University, one of the lead authors on the study, the findings are "an important step forward" in the understanding of anxiety disorders and how genes contribute to mental conditions.

Anxiety refers to the anticipation of perceived future threats. In anxiety disorders, these concerns are out of proportion to the actual anticipated event, leading to distress and disability. Anxiety disorders often occur alongside other mental health disorders like depression. {module INSIDE STORY}

Only a third of those with anxiety disorders receive treatment. Some forms of psychotherapy, such as cognitive-behavioral therapy, have proved effective, as have medications such as selective serotonin reuptake inhibitors. In other fields of medicine, genetic studies have led to precision medicine approaches--tailoring drug treatment to patients' individual genetic and biochemical profiles--for a number of diseases. The researchers hope more genetic insight will lead to similar approaches for anxiety.

The findings for the African American participants are especially important, says Levey. "Minorities are underrepresented in genetic studies, and the diversity of the Million Veteran Program was essential for this part of the project. The genetic variant we identified occurs only in individuals of African ancestry, and would have been completely missed in less diverse cohorts."

The study produced the first genome-wide significant findings on anxiety in African ancestry, notes Levey. About 18% of MVP participants are African American.

"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."

Finding the genetic underpinnings of mental health disorders is the primary goal of the Million Veteran Program, a compilation of health and genetic data on U.S. military veterans run by the U.S. Veterans Administration. The research team analyzed the program's data and zeroed in on six variants linked to anxiety. Five were found in European Americans and one found only in African Americans. Gene variants at these genome locations could increase anxiety risk, say the scientists.

The anxiety-related genome locations also show overlap with other psychiatric conditions. One of the identified locations has previously been linked with risk for bipolar disorder and schizophrenia. The study also shows a genetic overlap between anxiety symptoms and depression, PTSD (which is related to anxiety), and neuroticism--a personality trait that has been shown to increase the risk for anxiety and related disorders. The results support the idea that overlap with these other traits is at least partially due to a significant genetic commonality, according to the researchers.

MVP is a national, voluntary research program funded by VA's Office of Research and Development. It is one of the world's largest databases of health and genomic information. MVP partners with veterans receiving care in VA to study how genes affect health. As of November 2019, MVP had enrolled more than 800,000 veterans.

"MVP has enormous potential for increasing our knowledge about the genetics underlying a huge range of traits, including psychiatric traits. It is one of the best samples in the world for this purpose," said Dr. Joel Gelernter, also of the VA Connecticut Healthcare Center and Yale University. Gelernter is one of the senior authors of the work, together with Dr. Murray Stein of the VA San Diego Healthcare System and University of California San Diego.