Large-Scale Analysis Links Two of 20 Candidate Genes to Panic Disorder

Large-Scale Analysis Links Two of 20 Candidate Genes to Panic Disorder

Posted: January 15, 2016

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.

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An analysis of data pooled from 62 previous studies links variations in two genes to panic disorder among people with European ancestry, but also underscores the disorder’s genetic complexity.

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.

The meta-analysis revealed no significant genetic associations with panic disorder among people of Asian ancestry. The researchers also considered whether certain genetic variations might be linked to panic disorder only in men or women (women are twice as likely as men to experience the disorder). But they found no significant associations in those analyses. Likewise, no genetic associations were found in analyses that considered the effects of agoraphobia, a severe anxiety disorder that affects about one-third of people with panic disorder.
 
The researchers say a wide range of biological pathways likely influence individuals’ susceptibility to panic disorder, and large-scale, genome-wide studies involving many people will be needed to better understand its complex genetics.
Friday, January 15, 2016

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.

The meta-analysis revealed no significant genetic associations with panic disorder among people of Asian ancestry. The researchers also considered whether certain genetic variations might be linked to panic disorder only in men or women (women are twice as likely as men to experience the disorder). But they found no significant associations in those analyses. Likewise, no genetic associations were found in analyses that considered the effects of agoraphobia, a severe anxiety disorder that affects about one-third of people with panic disorder.
 
The researchers say a wide range of biological pathways likely influence individuals’ susceptibility to panic disorder, and large-scale, genome-wide studies involving many people will be needed to better understand its complex genetics.