Most psychiatric disorders share a small number of genetic risk factors, VCU study shows

Environment appears to influence few disorders

RICHMOND, Va. – In the most extensive and comprehensive study of its kind, researchers at Virginia Commonwealth University have demonstrated that the most common psychiatric and drug abuse disorders in both men and women can be traced to a small number of dimensions of genetic risk, which also influences the combination of disorders that tends to affect the same person.

The study, published in the September issue of the Archives of General Psychiatry, examined the similarities, for men and women, of the underlying genetic and environmental risk factors for a broad array of syndromes, including major depression, anxiety, phobia, drug dependence and abuse, alcohol dependence, adult antisocial behavior and conduct disorder. The findings lend further support to a growing body of evidence that suggests a small number of genetic factors are linked to various psychiatric and drug abuse disorders.

Using personal interviews that ranged over nine years in some cases, researchers assessed 5,600 male and female twins from same-sex pairs registered with VCU's Mid-Atlantic Twin Registry. 

Researchers frequently use identical and fraternal twins to study the impact of genetic and environmental factors on various health and behavior issues because twins share the same genes. In identical twins, the genes are 100 percent identical. Fraternal twins share 50 percent of their genes, or about the same as typical siblings.

In this study, researchers identified four major sets of genetic risk factors for the seven common disorders:

  • One genetic factor had the most significant impact on "externalizing disorders," which include alcohol dependence, drug abuse and dependence, adult antisocial behavior and conduct disorder.

  • A separate genetic factor had the most significant impact on "internalizing disorders," which include major depression, generalized anxiety disorder and phobia.

  • Substantial disorder-specific genetic factors were seen only for the two substance abuse disorders: one genetic factor for alcohol dependence and one genetic factor for drug abuse/dependence.  

The results showed that a shared environment affected only conduct disorder significantly and, more modestly, adult antisocial behavior.

"Most common psychiatric and drug abuse disorders are affected by two broad sets of genetic risk factors," says psychiatric geneticist Kenneth S. Kendler, M.D., professor of psychiatry and director of the Virginia Institute for Psychiatric and Behavioral Genetics at VCU. Kendler was the lead author on the study.

"One set of those genetic factors impacts on the risk for that group of syndromes that causes people to be miserable – those "internalizing" syndromes such as major depression and anxiety disorders," Kendler said. "The other set of genetic factors impacts on that group of syndromes that causes people to make others around them miserable. We call these "externalizing" disorders, including such conditions as antisocial personality and drug dependence."

Kendler said researchers were surprised that the data did not show differences in the pattern of risk factors between men and women. The two sexes differ quite a bit in terms of rates of predisposition to the two groups of disorders: Females are more prone to internalizing disorders, and males are more prone to externalizing disorders. "Despite large differences in prevalence rates for nearly all the disorders, the same configuration of underlying risk factors accounted for the patterns of the disorders in men and women," Kendler said. "From a genetic-epidemiologic perspective, these results suggest that the most pronounced sex differences are in the level of liability required to manifest clinical illness rather than in the underlying pattern of the risk factors themselves." 

Kendler said the next step will be molecular studies that look for the specific genes responsible for causing the disorders.  In addition, he said, further studies will look at the role personality and emotion play on mediating the genetic factors.

"As we look for the genes for these common disorders, the results raise the question of whether it would be more efficient to focus on groups of disorders with shared genetic risk rather than on individual disorders," he said.

The research was supported by grants from the National Institutes of Health.

About the Virginia Institute for Psychiatric and Behavioral Genetics

The Virginia Institute for Psychiatric and Behavioral Genetics is a multi-disciplined, integrated research program of VCU’s Departments of Psychiatry and Human Genetics, focused on identifying genes and environments that cause psychiatric diseases and behavioral differences. For more, see

About VCU and VCU Medical Center

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 226 degree and certificate programs in the arts, sciences and humanities. Sixty-seven of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University comprise VCU Medical Center, one of the nation’s leading academic medical centers. For more, see