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Genetic Evidence Indicates Post-Traumatic Stress Disorder Risk Is Partially Heritable

NEW YORK (GenomeWeb) – A consortium of researchers has found molecular genetic evidence in data from more than 20,000 individuals that post-traumatic stress disorder risk is partially heritable.

In the US, about one in nine women and one in 20 men will meet the diagnostic criteria for PTSD during their life. The condition, which is set off by a traumatic event, is marked by re-experiencing the event, avoidance of related stimuli, and a chronic feeling of being on edge. PTSD is also associated with increased suicide, substance abuse, and hospitalization risk. While PTSD is triggered by an external event, there have been suspicions that susceptibility to it might be genetically influenced.

"We know from lots of data — from prisoners of war, people who have been in combat, and from rape victims — that many people exposed to even extreme traumatic events do not develop PTSD. Why is that? We believe that genetic variation is an important factor contributing to this risk or resilience," said senior author Karestan Koenen, a professor of psychiatric epidemiology at the Harvard T.H. Chan School of Public Health and a researcher at the Broad Institute, in a statement.

Koenen and other researchers from the Psychiatric Genomics Consortium PTSD Working Group combined genome-wide case-control molecular genetic data from 11 multi-ethnic studies to examine PTSD heritability. As they reported today in Molecular Psychiatry, they estimated a nearly 30 percent heritability for PTSD among women of European ancestry. There also appeared to be an overlap in genetic risk of PTSD and schizophrenia.

In particular, they gathered data from more than 20,000 subjects, including individual-level data from nine genome-wide association studies and SNP-level summary statistic data from two such studies, and broke it down by ancestry as well as by sex.

While they uncovered no variants that reached genome-wide significance for association with PTSD in transethnic or European-only ancestry analyses, they did find one variant in the KLHL1 gene on chromosome 13 that reached significance within African Americans. However, they were unable to replicate it in a cohort from the Army STARRS consortium.

Still, they used linkage disequilibrium score regression and genome-wide complex trait analysis to estimate a heritability of PTSD of 29 percent for women of European descent, which they noted was comparable to estimates from twin studies and to results for other psychiatric disorders. For males, however, the heritability estimate was lower, at 7 percent.

Koenen and colleagues noted that there are several possible explanations for why female heritability is higher than that of males, including sex-based differences in exposure to trauma, response to trauma, and reliability or validity of PTSD diagnoses.

They added that they were unable to derive a heritability estimate for African Americans as there are no twin studies drawing on primarily non-European ancestry populations; the linkage disequilibrium score regression and genome- wide complex trait analysis approaches rely on external data resources that are less common or non-existent for non-European ancestry populations; and as genotyping arrays may have a Euro-centric bias. This, they said, underscores the need for large, diverse genetic studies.

Additionally, polygenic risk scores derived using the open-source toolset PLINK among people of European ancestry suggested that PTSD risk overlaps with risk for schizophrenia and, to a lesser extent, bipolar disorder.

"There are interventions effective in preventing PTSD shortly after a person experiences a traumatic event. But they are too resource-intensive to give to everyone," first author Laramie Duncan, previously at the Broad and now at Stanford University, added. "Knowing more about people's genetic risk for PTSD may help clinicians target interventions more effectively and it helps us understand the underlying biological mechanisms."