By Alisa Lehman, Ph.D.

Fear and anxiety are part of a threat-response system that is essential for survival. But for up to one in three people this system can become dysregulated, leading to anxiety disorders like generalized anxiety disorder, panic disorder, and phobias.

Researchers have known these conditions have a genetic component and can run in families, but the exact genetic underpinnings have been hard to identify. Now, a new study, led by researchers from the Anxiety Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ANX), has identified dozens of new genetic variants linked to anxiety disorders, and data from millions of consented 23andMe research participants was used to confirm their findings.

The Hunt for Anxiety-Associated Genetic Variants

To find the genetic variants involved in complex traits like anxiety disorders, scientists need a lot of study participants. To get this large group, the researchers combined data from 36 different studies of people from Europe, the United States, and Australia. In total they had 122,225 people diagnosed with an anxiety disorder and 729,960 unaffected controls.

Then the researchers performed a genome-wide association meta-analysis, which scans the entire genome looking for genetic variants that are more common in people with anxiety disorders. By comparing the genomes of those with anxiety disorders to those without, the team identified 58 significant genetic variants associated with anxiety disorders.

Confirmation: The Critical Role of Replication

Finding genetic variants associated with anxiety disorders is just the first step. To be confident it’s a real association and not a statistical fluke, results must be replicated in a completely independent group of people.

This is where the 23andMe Research Institute came in. The researchers tested their 58 variants in a massive cohort of consented 23andMe research participants, which included 1,175,012 participants who self-reported having anxiety and 1,956,379 participants who reported they did not.

Of the 55 variants they could test, all showed the same direction effect as in the discovery study, and 51 were significantly replicated. This gives researchers high confidence that these genetic variants are genuinely associated with anxiety in this population.

A Critical Reminder About Ancestry Groups and Diversity

The study’s next step is an important lesson for the future of genetic research. The team attempted to replicate their findings using data from over 30,000 African American participants in the Million Veteran Program.

The result? Of the 53 variants tested in this cohort, only 27 (about 51%) showed the same effect, a rate no better than random chance.

This is not a flaw in the study; it is a crucial finding. It demonstrates that genetic discoveries made in one group (in this case, people of European descent) do not always reliably apply to other groups. This underscores the urgent need for diverse populations to participate in future genetic studies to ensure that the scientific and medical benefits of this research can be shared by everyone.

What Do These Genes Do?

Identifying the 58 genetic variants and replicating the finding was just the first step. Researchers also wanted to know what these variants do. Functional analysis provided a major clue.

The variants were found to be active in all major brain regions. More specifically, the results highlighted GABAergic signaling as a potential biological mechanism underlying anxiety disorders. GABA is the brain’s primary inhibitory neurotransmitter, meaning it is a chemical messenger that calms down brain activity.

This is particularly exciting because many current anti-anxiety medications (like benzodiazepines) work by targeting this exact system. And there are also other genes in the GABAergic signaling pathway that could be good targets for future drugs to treat anxiety disorders.

This study represents a major leap in our understanding of the genetic basis of anxiety. These 58 variants provide a foundational genetic basis that can guide scientists in future investigations into the biological pathways that lead to anxiety, with the ultimate hope of developing new and better treatments.

Learn more about 23andMe Research here. Research participants provided informed consent and volunteered to participate in the research online, under a protocol approved by the external, independent review board AAHRPP-accredited Salus IRB.

About the Author

Alisa Lehman, Ph.D. — Sr. Manager, Product Science

Dr. Alisa Lehman has been working at 23andMe since 2015 creating scientifically accurate, consumer-friendly genetic reports on ancestry and health topics. Dr. Lehman holds a B.S. in Biology from MIT, and a Ph.D. in Biological Sciences from Stanford University.