Summary: A new study reports molecular genetics can play an influential role in the risk of developing PTSD following a traumatic event.

Source: Harvard.

A large new study from the Psychiatric Genomics Consortium provides the first molecular genetic evidence that genetic influences play a role in the risk of getting Posttraumatic Stress Disorder (PTSD) after trauma.

The report extends previous findings that showed that there is some shared genetic overlap between PTSD and other mental disorders such as schizophrenia. It also finds that genetic risk for PTSD is strongest among women.

The study will be published April 25, 2017 in Molecular Psychiatry.

“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, professor of psychiatric epidemiology at Harvard T.H. Chan School of Public Health who leads the Global Neuropsychiatric Genomics Initiative of the Stanley Center for Psychiatric Research at Broad Institute.

PTSD is a common and debilitating mental disorder that occurs after a traumatic event. Symptoms include re-experiencing the traumatic event, avoiding event-related stimuli, and chronic hyperarousal. In the U.S., one in nine women and one in twenty men will meet the criteria for a PTSD diagnosis at some point in their lives. The societal impact is large, including increased rates of suicide, hospitalization, and substance use.

The new study–by bringing together data from more than 20,000 people participating in 11 multi-ethnic studies around the world–builds a strong case for the role of genetics in PTSD, which had been previously documented on a smaller scale in studies of twins.

Using genome-wide genomic data, the researchers found that, among European American females, 29% of the risk for developing PTSD is influenced by genetic factors, which is comparable to that of other psychiatric disorders. In contrast, men’s genetic risk for PTSD was substantially lower.

The researchers found strong evidence that people with higher genetic risk for several mental disorders–including schizophrenia, and to a lesser extent bipolar and major depressive disorder–are also at higher genetic risk for developing PTSD after a traumatic event.

“PTSD may be one of the most preventable of psychiatric disorders,” said first author Laramie Duncan, who did part of the research while at the Broad Institute and is now at Stanford University. “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. 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.”

Harvard Chan School’s Andrea Roberts, research associate in the Department of Social and Behavioral Sciences, was also a co-author.

Funding: This study was conducted by the Psychiatric Genomics Consortium PTSD Working Group and was supported by the National Institute of Mental Health (U01MH094432; U01MH094432), Cohen Veterans Bioscience, One Mind, and the Stanley Center for Psychiatric Research.

Source: Marge Dwyer – Harvard
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Full open access research for “Largest GWAS of PTSD (N=20,070) Yields Genetic Overlap with Schizophrenia and Sex Differences in Heritability” by Laramie E. Duncan, Andrew Ratanatharathorn, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Allison E. Ashley-Koch, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan Bisson, Bekh Bradley, Chia-Yen Chen, Shareefa Dalvie, Lindsay A. Farrer, Sandro Galea, Melanie E. Garrett, Joel E. Gelernter, Guia Guffanti, Michael A. Hauser, Eric O. Johnson, Ronald C. Kessler, Nathan A. Kimbrel, Anthony King, Nastassja Koen, Henry R. Kranzler, Mark W. Logue, Adam X. Maihofer, Alicia R. Martin, Mark W. Miller, Rajendra A. Morey, Nicole R. Nugent, John P. Rice, Stephan Ripke, Andrea L. Roberts, Nancy L. Saccone, Jordan W. Smoller, Dan J. Stein, Murray B. Stein, Jennifer A. Sumner, Monica Uddin, Robert J. Ursano, Derek E. Wildman, Rachel Yehuda, Hongyu Zhao, Mark J. Daly, Israel Liberzon, Kerry J. Ressler, Caroline M. Nievergelt, and Karestan C. Koenen in Molecular Psychiatry. Published online April 25 2017 doi:10.1038/MP.2017.77

Abstract

Largest GWAS of PTSD (N=20,070) Yields Genetic Overlap with Schizophrenia and Sex Differences in Heritability

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case–control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD.

Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero).

We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations.

Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD—for both European- and African-American individuals—and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes.

Publication of summary statistics for ~10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples.

As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

“Largest GWAS of PTSD (N=20,070) Yields Genetic Overlap with Schizophrenia and Sex Differences in Heritability” by Laramie E. Duncan, Andrew Ratanatharathorn, Allison E. Aiello, Lynn M. Almli, Ananda B. Amstadter, Allison E. Ashley-Koch, Dewleen G. Baker, Jean C. Beckham, Laura J. Bierut, Jonathan Bisson, Bekh Bradley, Chia-Yen Chen, Shareefa Dalvie, Lindsay A. Farrer, Sandro Galea, Melanie E. Garrett, Joel E. Gelernter, Guia Guffanti, Michael A. Hauser, Eric O. Johnson, Ronald C. Kessler, Nathan A. Kimbrel, Anthony King, Nastassja Koen, Henry R. Kranzler, Mark W. Logue, Adam X. Maihofer, Alicia R. Martin, Mark W. Miller, Rajendra A. Morey, Nicole R. Nugent, John P. Rice, Stephan Ripke, Andrea L. Roberts, Nancy L. Saccone, Jordan W. Smoller, Dan J. Stein, Murray B. Stein, Jennifer A. Sumner, Monica Uddin, Robert J. Ursano, Derek E. Wildman, Rachel Yehuda, Hongyu Zhao, Mark J. Daly, Israel Liberzon, Kerry J. Ressler, Caroline M. Nievergelt, and Karestan C. Koenen in Molecular Psychiatry. Published online April 25 2017 doi:10.1038/MP.2017.77