Dataset Information

Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury.

ABSTRACT: Traumatic brain injury (TBI) contributes to the increased rates of suicide and post-traumatic stress disorder in military personnel and veterans, and it is also associated with the risk for neurodegenerative and psychiatric disorders. A cross-phenotype high-resolution polygenic risk score (PRS) analysis of persistent post-concussive symptoms (PCS) was conducted in 845 U.S. Army soldiers who sustained TBI during their deployment. We used a prospective longitudinal survey of three brigade combat teams to assess deployment-acquired TBI and persistent physical, cognitive, and emotional PCS. PRS was derived from summary statistics of large genome-wide association studies of Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, and major depressive disorder (MDD); and for years of schooling, college completion, childhood intelligence, infant head circumference (IHC), and adult intracranial volume. Although our study had more than 95% of statistical power to detect moderate-to-large effect sizes, no association was observed with neurodegenerative and psychiatric disorders, suggesting that persistent PCS does not share genetic components with these traits to a moderate-to-large degree. We observed a significant finding: subjects with high IHC PRS recovered better from cognitive/emotional persistent PCS than the other individuals (R2?=?1.11%; p?=?3.37?×?10-3). Enrichment analysis identified two significant Gene Ontology (GO) terms related to this result: GO:0050839?Cell adhesion molecule binding (p?=?8.9?×?10-6) and GO:0050905?Neuromuscular process (p?=?9.8?×?10-5). In summary, our study indicated that the genetic predisposition to persistent PCS after TBI does not have substantial overlap with neurodegenerative and psychiatric diseases, but mechanisms related to early brain growth may be involved.

SUBMITTER: Polimanti R

PROVIDER: S-EPMC5314978 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury.

Polimanti Renato R Chen Chia-Yen CY Ursano Robert J RJ Heeringa Steven G SG Jain Sonia S Kessler Ronald C RC Nock Matthew K MK Smoller Jordan W JW Sun Xiaoying X Gelernter Joel J Stein Murray B MB

Journal of neurotrauma 20160825 4

Traumatic brain injury (TBI) contributes to the increased rates of suicide and post-traumatic stress disorder in military personnel and veterans, and it is also associated with the risk for neurodegenerative and psychiatric disorders. A cross-phenotype high-resolution polygenic risk score (PRS) analysis of persistent post-concussive symptoms (PCS) was conducted in 845 U.S. Army soldiers who sustained TBI during their deployment. We used a prospective longitudinal survey of three brigade combat t ...[more]

PMID: 27439997

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Project description:Studies have suggested that sickle cell trait elevates the risks of exertional rhabdomyolysis and death. We conducted a study of sickle cell trait in relation to these outcomes, controlling for known risk factors for exertional rhabdomyolysis, in a large population of active persons who had undergone laboratory tests for hemoglobin AS (HbAS) and who were subject to exertional-injury precautions.We used Cox proportional-hazards models to test whether the risks of exertional rhabdomyolysis and death varied according to sickle cell trait status among 47,944 black soldiers who had undergone testing for HbAS and who were on active duty in the U.S. Army between January 2011 and December 2014. We used the Stanford Military Data Repository, which contains comprehensive medical and administrative data on all active-duty soldiers.There was no significant difference in the risk of death among soldiers with sickle cell trait, as compared with those without the trait (hazard ratio, 0.99; 95% confidence interval [CI], 0.46 to 2.13; P=0.97), but the trait was associated with a significantly higher adjusted risk of exertional rhabdomyolysis (hazard ratio, 1.54; 95% CI, 1.12 to 2.12; P=0.008). This effect was similar in magnitude to that associated with tobacco use, as compared with no use (hazard ratio, 1.54; 95% CI, 1.23 to 1.94; P<0.001), and to that associated with having a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30.0 or more, as compared with a BMI of less than 25.0 (hazard ratio, 1.39; 95% CI, 1.04 to 1.86; P=0.03). The effect was less than that associated with recent use of a statin, as compared with no use (hazard ratio, 2.89; 95% CI, 1.51 to 5.55; P=0.001), or an antipsychotic agent (hazard ratio, 3.02; 95% CI, 1.34 to 6.82; P=0.008).Sickle cell trait was not associated with a higher risk of death than absence of the trait, but it was associated with a significantly higher risk of exertional rhabdomyolysis. (Funded by the National Heart, Lung, and Blood Institute and the Uniformed Services University of the Health Sciences.).

Project description:ImportanceUnderstanding suicide ideation (SI) during combat deployment can inform prevention and treatment during and after deployment.ObjectiveTo examine associations of sociodemographic characteristics, lifetime and past-year stressors, and mental disorders with 30-day SI among a representative sample of US Army soldiers deployed in Afghanistan.Design, setting, and participantsIn this survey study, soldiers deployed to Afghanistan completed self-administered questionnaires in July 2012. The sample was weighted to represent all 87 032 soldiers serving in Afghanistan. Prevalence of lifetime, past-year, and 30-day SI and mental disorders was determined. Logistic regression analyses examined risk factors associated with SI. Data analyses for this study were conducted between August 2018 and August 2019.Main outcomes and measuresSuicide ideation, lifetime and 12-month stressors, and mental disorders were assessed with questionnaires. Administrative records identified sociodemographic characteristics and suicide attempts.ResultsA total of 3957 soldiers (3473 [weighted 87.5%] male; 2135 [weighted 52.6%] aged ≤29 years) completed self-administered questionnaires during their deployment in Afghanistan. Lifetime, past-year, and 30-day SI prevalence estimates were 11.7%, 3.0%, and 1.9%, respectively. Among soldiers with SI, 44.2% had major depressive disorder (MDD) and 19.3% had posttraumatic stress disorder in the past 30-day period. A series of analyses of the 23 grouped variables potentially associated with SI resulted in a final model of sex; race/ethnicity; lifetime noncombat trauma; past 12-month relationship problems, legal problems, and death or illness of a friend or family member; and MDD. In this final multivariable model, white race/ethnicity (odds ratio [OR], 3.1 [95% CI, 1.8-5.1]), lifetime noncombat trauma (OR, 2.1 [95% CI, 1.1-4.0]), and MDD (past 30 days: OR, 31.8 [95% CI, 15.0-67.7]; before past 30 days: OR, 4.9 [95% CI, 2.5-9.6]) were associated with SI. Among the 85 soldiers with past 30-day SI, from survey administration through 12 months after returning from deployment, 6% (5 participants) had a documented suicide attempt vs 0.14% (6 participants) of the 3872 soldiers without SI.Conclusions and relevanceThis study suggests that major depressive disorder and noncombat trauma are important factors in identifying SI risk during combat deployment.

Project description:IntroductionUnderstanding how soldiers die after separation from military service, particularly those who die shortly after separating from service, may help to identify opportunities to ease transitions to civilian life.Materials and methodsMortality data were analyzed for male U.S. Army soldiers who died within 18 months of their separation from service (from 1999 to 2011). Descriptive statistics were calculated for natural, accidental, suicidal, homicidal, undetermined, and legal/operation of war deaths and were stratified by age, component, time in service, and type of discharge. Crude and age-adjusted mortality rates, standardized for all years using the 2004 Regular Army population, were also calculated. The Public Health Review Board of the U.S. Army Public Health Center approved this study as Public Health Practice.ResultsOf the 1,884,653 male soldiers who separated from service during the study period, 3,819 died within 18 months of separation. A majority of all separations were Reserve or National Guard (58%), and 62% of decedents were in the Reserve or National Guard. Deaths from natural causes (38%) were the most common, followed by accident deaths (34%), suicides (20%), homicides (6%), undetermined deaths (2%), and legal/operation of war deaths (<1%). For overall mortality, age-adjusted rates were higher among the male U.S. population when compared to male soldiers who had separated from the Army.ConclusionsThe time period immediately following separation from the Army presents a unique challenge for many soldiers. Developing more effective pre-separation prevention programs that target specific risks requires knowing the causes of death for natural deaths, suicides, and accidents. Over half of all deaths occurring shortly after separation from service are preventable. Continued surveillance of specific causes of preventable deaths following separation can improve pre-separation prevention programs and transitions to post-service care.

Project description:BackgroundAlthough the majority of active duty U.S. Army soldiers are full-time personnel in the Active Component (AC), a substantial minority of soldiers on active duty are in the Reserve Components (RCs). These "citizen-soldiers" (Army National Guard and Army Reserve) represent a force available for rapid activation in times of national need. RC soldiers experience many of the same stressors as AC soldiers as well as stressors that are unique to their intermittent service. Despite the important role of RC soldiers, the vast majority of military mental health research focuses on AC soldiers. One important goal of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) is to address this gap. Here we examine predictors of suicide attempts among activated RC soldiers.MethodsThis longitudinal, retrospective cohort study used individual-level person-month records from Army and Department of Defense administrative data systems to examine socio-demographic, service-related, and mental health predictors of medically documented suicide attempts among activated RC soldiers during 2004-2009. Data from all 1103 activated RC suicide attempters and an equal-probability sample of 69,867 control person-months were analyzed using a discrete-time survival framework.ResultsEnlisted soldiers comprised 84.3% of activated RC soldiers and accounted for 95.7% of all activated RC suicide attempts (overall rate = 108/100,000 person-years, more than four times the rate among officers). Multivariable predictors of enlisted RC suicide attempts included being female, entering Army service at age ≥ 25, current age < 30, non-Hispanic white, less than high school education, currently married, having 1-2 years of service, being previously deployed (vs. currently deployed), and history of mental health diagnosis (particularly when documented in the previous month). Predictors among RC officers (overall rate = 26/100,000 person-years) included being female and receiving a mental health diagnosis in the previous month. Discrete-time hazard models showed suicide attempt risk among enlisted soldiers was inversely associated with time in service.ConclusionsRisk factors for suicide attempt in the RCs were similar to those previously observed in the AC, highlighting the importance of research and prevention focused on RC enlisted soldiers in the early phases of Army service and those with a recent mental health diagnosis.

Dataset Information

Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury.

Publications

Cross-Phenotype Polygenic Risk Score Analysis of Persistent Post-Concussive Symptoms in U.S. Army Soldiers with Deployment-Acquired Traumatic Brain Injury.

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