For people with panic disorder sudden attacks of fear can cause a range of symptoms including sweating, nausea and a feeling of being out of control. Worry about the next attack can be so intense that people avoid places where they have experienced panic in the past. Both genetic and environmental factors are thought to influence who develops the disorder, but researchers have struggled to tease out specific genetic variations related to increased risk.

Although no genes have been convincingly linked to risk for panic disorder, numerous studies have identified candidate genes that may be involved. In a massive meta-analysis study combining prior study results, published September 22 in the journal Molecular Psychiatry, researchers reconsidered the involvement of 20 candidate genes. The meta-analysis, which has greater statistical power than any single study, succeeded in linking variations in two genes with panic disorder among people with European ancestry.

The research team was led by 2008 Young Investigator Vincenzo De Luca, M.D., Ph.D., at the University of Toronto, and included 2006 Young Investigator Elisabeth B. Binder, M.D., Ph.D., at the Max Planck Institute of Psychiatry in Germany and 2002 and 2008 Young Investigator Jordan W. Smoller, M.D., at Massachusetts General Hospital. Dr. Aaron Howe of the University of Toronto was the first author of the paper reporting the team’s results.

The team analyzed data from a total of 62 previous studies, plus additional data from their own research. The researchers found that among people of European descent, variations in genes called TMEM132D and COMT were more common among people with panic disorder than they were in unaffected people. The COMT gene tells nerve cells how to manufacture an enzyme involved in activating the message-carrying neurotransmitters dopamine, epinephrine and norepinephrine. Variations in TMEM132D, which produces a protein on the surface of certain brain cells, have been linked to increased anxiety in clinical and animal studies.