Drill sergeants in competition. Photo: CC--US Army

Celiac.com 06/20/2016 - Are there genetic correlations between PTSD and mental disorders or immune-related disorders? What role does genetics play in PTSD, if any? A team of researchers recently set out to discover genetic loci associated with the lifetime risk for PTSD in 2 groups from the Army Study to Assess Risk and Resilience in Service members (Army STARRS).

The research team included Murray B. Stein, MD, MPH, Chia-Yen Chen, ScD; Robert J. Ursano, MD; Tianxi Cai, ScD; Joel Gelernter, MD; Steven G. Heeringa, PhD; Sonia Jain, PhD; Kevin P. Jensen, PhD; Adam X. Maihofer, MS; Colter Mitchell, PhD; Caroline M. Nievergelt, PhD; Matthew K. Nock, PhD; Benjamin M. Neale, PhD; Renato Polimanti, PhD; Stephan Ripke, MD5; Xiaoying Sun, MS; Michael L. Thomas, PhD; Qian Wang, PhD; Erin B. Ware, PhD; Susan Borja, PhD; Ronald C. Kessler, PhD; Jordan W. Smoller, MD, ScD; for the Army Study to Assess Risk and Resilience in Service-members (STARRS).

They are variously affiliated with the Department of Psychiatry, and the Department of Family Medicine and Public Health, UCSD, La Jolla, the Psychiatry Service of the Veterans Affairs San Diego Healthcare System, San Diego, California, the Department of Psychiatry at Massachusetts General Hospital and Harvard Medical School, Boston, the Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, the Department of Psychiatry, Uniformed Services University of the Health Sciences in Bethesda, Maryland, the Harvard T. H. Chan School of Public Health, Boston, Massachusetts, the Department of Psychiatry, Genetics, and Neurobiology at Yale University in New Haven, Connecticut, the Institute for Social Research, University of Michigan, Ann Arbor, the Department of Psychology, Harvard University, Cambridge, Massachusetts, the Department of Computational Biology and Bioinformatics, Graduate School of Arts and Sciences at Yale University, New Haven, Connecticut, the National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, and with the Department of Health Care Policy, Harvard Medical School, Boston, Massachusetts

The study looked at subjects from two coordinated genome-wide association studies of mental health in the US military.

The first study, the New Soldier Study (NSS), included 3,167 unique patients with PTSD and 4,607 trauma-exposed control subjects. The NSS data were collected from February 1, 2011, to November 30, 2012.

The second study, the Pre/Post Deployment Study (PPDS), included 947 unique patients with PTSD and 4,969 trauma-exposed control subjects. The PDDS data were collected from January 9 to April 30, 2012.

The primary analysis compared lifetime DSM-IV PTSD cases with trauma-exposed controls without lifetime PTSD. Data were analyzed from March 18 to December 27, 2015. The team used logistic regression models to conduct association analyses for PTSD among European, African, and Latino Americans by study, followed by meta-analysis. They also estimated heritability, genetic correlation and pleiotropy with other psychiatric and immune-related disorders.

The NSS population of 7,774 patients was just over 80% male, and about 21 years old, while the PPDS population of 5,916 patients was 94.4% male, and about 26.5 years old.

A genome-wide significant locus was found in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR], 1.62; 95% CI, 1.37-1.92; P = 2.34 × 10−8) and persisted after adjustment for cumulative trauma exposure (adjusted OR, 1.64; 95% CI, 1.39-1.95; P = 1.18 × 10−8) in the African American samples from the NSS.

They also found a genome-wide significant locus in or near ZNF626 on chromosome 19 (rs11085374; OR, 0.77; 95% CI, 0.70-0.85; P = 4.59 × 10−8) in the European American samples from the NSS. They did not find any similar results for either single-nucleotide polymorphism in the corresponding ancestry group from the PPDS sample, in other ancestral groups, or in transancestral meta-analyses.

Overall, they saw no significant evidence for single-nucleotide polymorphism–based heritability, and they found no significant genetic correlations between PTSD and 6 mental disorders or 9 immune-related disorders.

They did find significant evidence of a single-gene linking PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis.

Beyond that, they didn't find not much to support any connection to specific gene locations.

The researchers are calling for additional studies "to replicate the genome-wide significant association with ANKRD55—associated in prior research with several autoimmune and inflammatory disorders—and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis."

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