Women have a higher genetic risk for PTSD according to VCU study and Swedish researchers

By Olivia Trani

Women are twice as likely as men to develop post-traumatic stress disorder, but the factors that contribute to this disparity remain largely unresolved. A research team led by Virginia Commonwealth University and Lund University in Sweden conducted the largest PTSD study of twin sisters to date to shed light on how genetics may play a role. Their results, published Tuesday in the American Journal of Psychiatry, are the first to show that women have a higher genetic risk for the disorder than men.

Analyzing health data from over 16,000 twin pairs and 376,000 sibling pairs, the research team found that the heritability for PTSD was 7 percentage points higher in women (35.4%) than in men (28.6%). They also found evidence that genes that account for heritable risk for PTSD differ between the two sexes.

The researchers say their findings could inform strategies for PTSD prevention and intervention after a traumatic event, as well as help address the stigma associated with women’s mental health.

“Women are at higher risk of developing PTSD than men, even when controlling for type of trauma, income level, social support, and other environmental factors. Some of the theories as to why this is frankly unfair to women, such as attributing the sex difference to a weakness or lack of ability to cope,” said Ananda B. Amstadter, Ph.D., a professor at the VCU School of . of the departments of Psychiatry and Human Genetics and lead author of the study. “I think this study may help shift the narrative that people may have an inherited biological risk for PTSD and that this genetic risk is more big on women.”

Nearly 70% of the global population is exposed to at least one traumatic event in their lifetime, such as physical or sexual assault, a motor vehicle accident, exposure to combat, or a natural disaster. About 6% of those exposed to trauma develop PTSD. Amstadter’s research focuses on understanding the conditions that can increase or decrease a person’s risk of experiencing PTSD, particularly how a person’s genes affect their risk.

“If you think of risk for PTSD as a pie chart, we’re trying to better understand what factors make up the pieces of that pie,” she said. “Some of the risk is influenced by a person’s environment, such as the experiences they have while growing up. In turn, part of the risk will be influenced by the genes they inherit from their parents.”

Previous research has looked at how genes influence the likelihood of developing PTSD, but the study conducted by Amstadter and her colleagues is the first of its kind to investigate how genetic risk varies by sex.

For this project, the research team examined anonymized clinical data from Swedish population-based registries. Their analysis consisted of more than 400,000 pairs of twins or siblings born up to two years apart in Sweden between 1955 and 1980. Twin and sibling studies, because of their genetic similarities, can help researchers determine how a person’s genes affect their risk for mental illness.

“Every time a person within this age group interacts with Sweden’s healthcare system, whether it’s visiting a primary care doctor, filling a prescription or going to hospital, that information is recorded in their national registers. These types of data are a really powerful tool for addressing questions related to genetic risk for medical conditions,” Amstadter said. “Previous studies of PTSD involving twins and siblings have typically included only a few thousand individuals. Because because our sample size was so large in comparison, we were able to make calculations with a higher degree of confidence.”

Through statistical modeling, the researchers calculated how much a person’s genetic makeup affected their likelihood of developing PTSD after a traumatic event. Finding that PTSD was 35.4% heritable in women but only 28.6% heritable in men, they showed that women have a higher biological risk for PTSD.

Their models also found that PTSD-related genes were highly correlated (0.81) but not completely the same between men and women. This suggests that the genetic basis of sex hormones, such as testosterone, estrogen and progesterone, may be involved in the development of PTSD. The research team is collaborating with the Psychiatric Genomics Consortium to identify molecular genetic variants that may contribute to sex-specific risk pathways.

Amstadter conducted the research at the Virginia Institute for Psychiatric and Behavioral Genetics at VCU along with co-authors Shannon Cusack, Ph.D., a postdoctoral researcher; and Kenneth Kendler, MD, institute director, professor of psychiatry and distinguished researcher. They collaborated with Lund University co-authors Sara Lönn, Ph.D.; Jan Sundquist, MD, Ph.D.; and Kristina Sundquist, MD, Ph.D.