Genes Elucidate Why Anxiety And Depression Often Coexist

A genome-wide analysis of approximately 200,000 military veterans has revealed six genetic variants linked to anxiety. Some of the variants associated with anxiety had previously been implicated as risk factors for bipolar disorder, post-traumatic stress disorder, and schizophrenia.

“This is the richest set of results for the genetic basis of anxiety to date. 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,”

says co-lead author Joel Gelernter, a professor of psychiatry, of genetics, and of neuroscience at Yale University.

Genetic Architecture Of Anxiety

The new study[1] further contributes the first convincing molecular explanation for why anxiety and depression often coexist. There has been no explanation for the comorbidity of anxiety and depression and other mental health disorders, but now we have evidence for 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 US military veterans run by the US Veterans Administration.

The research team analyzed the program’s data and zeroed in on six variants linked to anxiety. Researchers found five in European Americans and one only in African Americans.

“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 1 in 10 Americans,”

says senior author Murray Stein, San Diego VA staff psychiatrist and professor of psychiatry and of family medicine and public health at the University of California, San Diego.

Estrogen Receptors

Researchers found some variants 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 might help explain why women are more than twice as likely as men to suffer from anxiety disorders, researchers stressed that they identified the variant affecting estrogen receptors in a veteran cohort made up mostly of men, and that further investigation is necessary.

Another of the newly discovered anxiety gene variants, MAD1L1, whose function researchers don’t fully understand, was also highly notable. 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 find important risk genes that are associated with risk for many psychiatric and behavioral traits for which we don’t have a good explanation,”

says co-lead author Daniel Levey, a postdoctoral associate.

[1] Daniel F. Levey, Joel Gelernter, Renato Polimanti, Hang Zhou, Zhongshan Cheng, Mihaela Aslan, Rachel Quaden, John Concato, Krishnan Radhakrishnan, Julien Bryois, Patrick F. Sullivan, the Million Veteran Program, and Murray B. Stein. Reproducible Genetic Risk Loci for Anxiety: Results From ∼200,000 Participants in the Million Veteran Program. American Journal of Psychiatry, 7 Jan 2020, https://doi.org/10.1176/appi.ajp.2019.19030256