Genome-wide Association Study Confirms PTSD Is in Part Genetically Determined

Studies of twins have documented that genetics account for 24% to 72% of the risk for post-traumatic stress disorder (PTSD) and that the genetic risk is two to three times higher for women than men. Such research has also shown that genetic influences on PTSD are shared with certain other psychiatric illnesses, particularly major depressive disorder.

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Karestan Koenen, PhD, a researcher with the Psychiatric and Neurodevelopmental Genetics Unit at Massachusetts General Hospital, is part of the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Workgroup, which aggregates genome-wide association data from multiple studies. In Molecular Psychiatry, the consortium reports its findings from the largest-ever genome-wide association study of PTSD.

Study Includes More Than 20,000 Individuals

Eleven research groups contributed 19 data sets for analysis:

• Seven studies of African Americans (N=9,691, 26% with PTSD)
• Nine studies of European Americans (N=9,954, 25% with PTSD)
• One study of Latinos/Hispanics (N=698, 14% with PTSD)
• Two studies of South Africans (N=387, 34% with PTSD)

Altogether, 20,730 adults were analyzed. Of the 15,548 control subjects without PTSD, 88% had been exposed to trauma.

Single-variant Analyses

Despite the very large sample, no single-nucleotide polymorphism achieved genome-wide significance in either an overall analysis or an analysis restricted to European Americans.

Findings in European Americans

Heritability Estimates

When the researchers conducted a meta-analysis of the nine European American studies, they found that among women the average heritability estimate was 29%, comparable to estimates for psychiatric disorders in twin studies.

In men, the estimate was not significantly different from zero. When women and men were analyzed together, the point estimate was 15%.

The researchers propose several potential explanations for the higher female heritability of PTSD:

• Rates of exposure to various types of trauma are known to vary by sex

• Particular types of trauma vary in the degree to which they are associated with PTSD

• There may be sex-based biological differences in responses to trauma and responses to the environmental factors that influence the development of PTSD

• The reliability and/or validity of PTSD diagnosis may differ by sex (e.g., cultural factors may discourage men from complaining of PTSD symptoms)

Cross-disorder Genetic Effects

There was strong evidence of shared genetic effects between PTSD and schizophrenia, and modest evidence of shared effects with major depressive disorder and bipolar disorder. The workgroup notes that other research has uncovered partially shared genetic effects across nearly all psychiatric disorders.

Findings in African Americans

In contrast to the analysis of European Americans, a meta-analysis of the seven studies of African Americans yielded no significant findings of heritability or shared genetic effects. This was true even though the African American and European American samples were about equally large.

However, the researchers state that this should not be taken as evidence that genetic influences in PTSD differ in the two racial groups. They highlight analytical disparities:

• Not all methods of polygenic data analysis are applicable to non-European populations

• Eurocentric bias is present in genotyping arrays

• There is greater genetic variation in the African portions of African American individuals' chromosomes, so more markers are needed to achieve the same proportion of genomic coverage

Clearly, there continues to be a need for large genetic studies in non-European populations. Otherwise, the researchers believe their findings are compelling, especially because they are consistent with the results of twin studies: although PTSD by definition requires an environmental exposure—trauma—it is also partly genetic in origin.

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