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Women are at Higher Genetic Risk for PTSD than Men, According to Large Twin-Sibling Study
In the largest twin-sibling study to date of the inherited biological risk of PTSD, researchers found additive genetic and unique environmental effects contributed to the disorder.
Women have a higher inherited biological risk for post-traumatic stress disorder (PTSD) than men, according to findings from the first research to identify genetic underpinnings for the disparity in incidence between the sexes. Women are more than twice as likely as men to develop the chronic and sometimes disabling condition, a difference that is independent of type of trauma, diagnostic criteria, and research methodology, study authors wrote in the American Journal of Psychiatry.
“Some of the theories as to why PTSD is more prevalent in women have frankly been unkind, such as attributing the sex difference to a weakness or lack of ability to cope,” lead author Ananda B. Amstadter, PhD, lead investigator and a professor in the Virginia Commonwealth University (VCU) School of Medicine’s departments of Psychiatry and Human and Molecular Genetics said in a news release. Amstadter and colleagues point to a legacy of twin studies that have found a moderately heritable component to PTSD with patterns across studies that suggest the heritability is higher among women than men. Environmental risk is also implicated in differences observed between the sexes but there is great variability in previous findings in both data sets related largely to population sample and study design, investigators wrote.
The research team cites evidence that PTSD is associated with more than $3 billion in productivity loss each year, and yet has rarely been the focus of the high-quality genetic epidemiologic research devoted to other psychiatric disorders, making it critical to advance understanding of its etiology.
The study team, led by Virginia Commonwealth University and Lund University in Sweden, designed its research to model genetic and environmental variance for PTSD and to test for quantitative and qualitative sex differences. Tapping the Swedish National Registries for anonymized data Amstadter et al assembled the largest known sample to date of both sexes among twins (N = 16 242 pairs) and siblings (N = 376 093 pairs). Using registry data, they explained, removes the potential bias of self-report or interviews and extending the analysis to sibling pairs allowed investigators to test for an influence of twin-specific environment in PTSD etiology.
Findings
According to the findings, “The best fit model suggested that additive genetic and unique environmental effects, but not the shared environment, contributed to PTSD.” The investigators found evidence for a quantitative sex effect, reporting heritability among women (35.4%) that was 7 points higher than among men (28.6%). The evidence for a qualitative sex effect was highly correlated (0.81) but not complete between the sexes, according to the results.
The findings are consistent with those of a previous Norwegian twin study, also led by Amstadter, which attributed 32% of PTSD variance to familial factors, though it lacked power to separate genetic and shared environmental contributions. The research team also stated that the significant quantitative sex difference is consistent with molecular genetic studies that have demonstrated higher PTSD heritability in women, patterns that have also been observed in major depression.
Amstadter et al acknowledge several study limitations, including use of registry-based ICD codes for diagnosis as PTSD diagnoses may conflate trauma exposure with PTSD itself. Trauma exposure has also been shown moderately heritable and varies by sex, which should be a consideration when interpreting the current findings. Also, diagnoses in this study were primarily made by primary care physicians rather than psychologists, potentially introducing variability in diagnostic precision.
Despite the limitations, however, the authors stand by their findings, noting they “provide robust evidence for moderate heritability of PTSD, sex-specific genetic contributions, and potential avenues for future research into hormonal and genetic influences on PTSD development and treatment response," they concdluded.
