Researchers at Yale’s Department of Psychiatry examined the genetic profiles of more than 1 million participants enrolled in multiple cohorts around the world. Using this large dataset, they discovered more than 100 genes associated with‘anxiety.
The results of the study were published in Nature Genetics.
Over 100 genes linked to anxiety discovered.
Anxiety disorders and symptoms affect many individuals with a negative impact on people’s quality of life. Understanding their genetic predisposition may have important implications for the development of more effective therapies and treatments to reduce the harmful consequences of anxiety symptoms.
“This effort highlights the ability of large-scale genetic studies to dissect the complex pathogenesis of anxiety symptoms by demonstrating how multiple genes acting on different brain functions contribute to defining individual genetic risk,” said Renato Polimanti, Ph.D., associate professor of psychiatry at Yale School of Medicine and lead author of the study.
“These findings open new possibilities for understanding the molecular basis of psychopathology and assessing the mechanisms responsible for the comorbidity between anxiety symptoms and other negative health outcomes.”
By integrating genetic information with other molecular characteristics, scientists have understood how genes can act on different brain structures to increase the risk of developing anxiety disorders and symptoms. They have also observed that some genes associated with anxiety symptoms may also predispose to other mental illnesses, including depression, schizophrenia, and bipolar disorder.
In line with the comorbidity of anxiety symptoms with physical health, the study also showed that genetic risk for anxiety symptoms is also related to non-psychiatric conditions. In particular, the strongest evidence was seen with gastrointestinal disorders and pain-related outcomes.
“By studying anxiety symptom disorders across five different ancestries for the first time, we were able to uncover the genetic architecture of anxiety disorders with greater genetic association power,” said Dr. Eleni Friligkou, a psychiatry resident in the Neuroscience Research Training Program and the study’s first author.
“Our efforts highlight the importance of increasing diversity in genetic studies to better understand the specific genetic correlates of anxiety disorders, but also to harness the power of cross-genetic discovery.”
The Genetic Basis of Anxiety
Another in-depth analysis of the genomes of nearly 200,000 military veterans has identified six genetic variants linked to anxiety, Yale researchers and colleagues at other institutions report in the American Journal of Psychiatry.
Some of the variants associated with anxiety have previously been implicated as risk factors for bipolar disorder, post-traumatic stress disorder, and schizophrenia.
New study provides first compelling molecular explanation for why anxiety and depression often coexist.
“This is the richest set of results for the genetic basis of anxiety to date,” said co-lead author Joel Gelernter, MD, PhD, the Foundations Fund Professor of Psychiatry and a professor of genetics and neuroscience at Yale. “There has been no explanation for the comorbidity of anxiety and depression and other mental health disorders, but here we find specific and shared genetic risks.”
Finding the genetic basis of mental health disorders is the primary goal of the Million Veteran Program, a collection of genetic and health data on U.S. military veterans managed by the U.S. Veterans Administration. The research team analyzed the program’s data and focused on six variants linked to anxiety. Five were found in European Americans and one in African Americans only.
“Although many studies have been conducted on the genetic basis of depression, far fewer have looked for variants linked to anxiety, a disorder that affects up to 1 in 10 Americans,” said lead author Murray Stein, a psychiatrist at the Department of Veterans Affairs in San Diego and professor emeritus of psychiatry, family medicine, and public health at UCSD.
Some variants have been linked to genes that help govern gene activity or, intriguingly, to a gene involved in the functioning of receptors for the sex hormone estrogen. While this finding could help explain why women are more than twice as likely as men to suffer from anxiety disorders, the researchers noted that the variant affecting estrogen receptors was identified in a cohort of veterans that was mostly male, and they said further investigation is needed.
Another newly discovered anxiety gene variant, MAD1L1, whose function is not yet fully understood, was also noteworthy. Variants of this gene have already been linked to bipolar disorder, post-traumatic stress disorder, and schizophrenia.
“One of the goals of this research is to identify important risk genes associated with risk for many psychiatric and behavioral traits for which we have no good explanation,” said Yale’s Daniel Levey, a postdoctoral associate and co-lead author of the study.
To conduct the study, the Yale researchers collaborated with colleagues at the Veteran Affairs Connecticut Healthcare System, the VA San Diego Healthcare System, and the University of California San Diego.
Gelernter said: “We have only just begun to tap into this rich vein.”
Social anxiety disorder may increase the risk of alcoholism
Further research published in Depression and Anxiety indicates that, unlike other anxiety disorders, social anxiety disorder may have a direct effect on alcoholism.
To conduct the study, researchers assessed alcoholism, social anxiety disorder, generalized anxiety disorder, panic disorder, agoraphobia, and specific phobias through interviews with 2,801 adult Norwegian twins.
Social anxiety disorder had the strongest association with alcoholism and predicted alcoholism above and beyond the effect of other anxiety disorders. Additionally, social anxiety disorder was linked to a higher risk of later alcoholism, while other anxiety disorders were not.
The findings suggest that interventions aimed at preventing or treating social anxiety disorder may have an additional beneficial effect in preventing alcoholism.
“Many individuals with social anxiety are not in treatment. This means that we have an underutilized potential, not only to reduce the burden of social anxiety, but also to prevent alcohol problems,” said lead author Dr. Fartein Ask Torvik, of the Norwegian Institute of Public Health. “Cognitive behavioral therapy with controlled exposure to feared situations has shown good results.”
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