Largest GWAS of anxiety traits reveals novel genetic variants

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gelernter joel80x106 - Largest GWAS of anxiety traits reveals novel genetic variants

Joel Gelernter

Findings of the largest genome-wide association study of anxiety traits to date have revealed new insights into genetic risk mechanisms shared by anxiety and related psychiatric disorders, researchers wrote in American Journal of Psychiatry.

“In this genetic study of anxiety in a large sample of United States veterans, we identified a novel set of genes that affects risk for anxiety,” Joel Gelernter, MD, of the department of psychiatry at Yale University School of Medicine, told Healio Psychiatry. “Using the results from the genome-wide association study (GWAS), we identified genetic overlap between anxiety and other traits and illnesses. These findings are giving us new ways to look at the biology that underlies anxiety disorder risk, and this should eventually lead to better targeting of treatments.”

According to Gelernter and colleagues, determining polygenic risk factors from large cohorts may inform an approach to identifying individuals predisposed to anxiety disorders. This would mirror recent strides made toward better understanding other aspects of medicine, including cardiology and medicine, using causal mutations and variants, they noted.

To examine genetic risk loci for anxiety and anxiety symptoms, the researchers analyzed data from approximately 200,000 U.S. veterans included in the Million Veteran Program — one of the world’s largest biobanks that includes medical, environmental and genetic data. The GWAS looked specifically at a continuous trait for anxiety, based on Generalized Anxiety Disorder 2-item scale (GAD-2) score, as the primary analysis. They used self-report of physician diagnosis of anxiety disorder as a secondary analysis.

On GAD-2 score, Gelernter and colleagues identified five genome-wide significant signals for European Americans, as well as one for African Americans. The novel genetic variants were found in and around several genes, some of which were identified in previous research as having known functional relationships with anxiety. Further, “these genes play roles in the hypothalamic-pituitary-adrenal axis, neuronal development and global regulation of gene expression,” the researchers wrote. They replicated these findings in the summary statistics of two major GWASs for anxiety and found evidence of significant genetic correlation between previous GWASs for anxiety, depression and neuroticism and GAD-2 score results. They also found significant genetic overlap with major depressive disorder and post-traumatic stress disorder.

“We were really excited to see these results,” Gelernter said. “We were not surprised to see the genetic overlap between anxiety, neuroticism and depression, but other results, such as the genetic relationship to lung cancer, were a little more surprising. Overall, there were many statistically significant and biologically meaningful results.” – by Joe Gramigna

Disclosures: Gelernter is named as co-inventor on a patent application related to genotype-guided dosing of opioid agonists. Please see the study for all other authors’ relevant financial disclosures.

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