Gulf War illness in the Gulf War Era Cohort and Biorepository: The Kansas and Centers for Disease Control definitions

Gifford, Elizabeth J.; Vahey, Jacqueline; Hauser, Elizabeth R.; Sims, Kellie J.; Efird, Jimmy T.; Dursa, Erin K.; Steele, Lea; Helmer, Drew A.; Provenzale, Dawn

doi:10.1016/j.lfs.2021.119454

Cited by 19 publications

(29 citation statements)

References 21 publications

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“…However, the frequency of symptoms reported by GWI cases was higher than generally observed in early GWI studies and substantially greater than the symptom burden required to meet Kansas GWI case criteria. This is consistent with other more recent studies of Gulf War veterans that have generally indicated that, over the years, 1990–1991 Gulf War veterans have reported an increasing burden both of chronic symptoms and of diagnosed health conditions [ 5 , 6 , 7 , 55 , 56 ]. In the current study, this increased symptom burden was also observed in controls, half of whom met CMI criteria.…”

Section: Discussionsupporting

confidence: 92%

“…This, in turn, would be expected to reduce their utility for accurately characterizing GWI cases for research and other purposes. Increased levels of morbidity observed in this and other studies supports the need for evidence-based revisions to existing GWI case definitions [ 6 , 57 , 58 , 59 ]. A primary consideration is that revised GWI criteria more accurately reflect present day symptoms and diagnosed health conditions associated with service in the 1990–1991 Gulf War in order to optimally distinguish GWI cases from noncases.…”

Section: Discussionsupporting

confidence: 72%

“…But after the successful execution of the Gulf War, a substantial number of military personnel returned home with difficult health problems that were not explained by familiar medical or psychiatric diagnoses [ 2 , 3 , 4 ]. This condition, now known as Gulf War illness (GWI), remains a serious problem for Gulf War veterans 30 years after the war [ 5 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Brain–Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990–1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study

et al. 2021

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The Boston University-based Gulf War Illness Consortium (GWIC) is a multidisciplinary initiative developed to provide detailed understanding of brain and immune alterations that underlie Gulf War illness (GWI), the persistent multisymptom disorder associated with military service in the 1990–1991 Gulf War. The core GWIC case-control clinical study conducted in-depth brain and immune evaluation of 269 Gulf War veterans (223 GWI cases, 46 controls) at three U.S. sites that included clinical assessments, brain imaging, neuropsychological testing, and analyses of a broad range of immune and immunogenetic parameters. GWI cases were similar to controls on most demographic, military, and deployment characteristics although on average were two years younger, with a higher proportion of enlisted personnel vs. officers. Results of physical evaluation and routine clinical lab tests were largely normal, with few differences between GWI cases and healthy controls. However, veterans with GWI scored significantly worse than controls on standardized assessments of general health, pain, fatigue, and sleep quality and had higher rates of diagnosed conditions that included hypertension, respiratory and sinus conditions, gastrointestinal conditions, and current or lifetime depression and post-traumatic stress disorder. Among multiple deployment experiences/exposures reported by veterans, multivariable logistic regression identified just two significant GWI risk factors: extended use of skin pesticides in theater (adjusted OR = 3.25, p = 0.005) and experiencing mild traumatic brain injury during deployment (OR = 7.39, p = 0.009). Gulf War experiences associated with intense stress or trauma (e.g., participation in ground combat) were not associated with GWI. Data and samples from the GWIC project are now stored in a repository for use by GWI researchers. Future reports will present detailed findings on brain structure and function, immune function, and association of neuroimmune measures with characteristics of GWI and Gulf War service.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

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Brain–Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990–1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study

et al. 2021

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“…The Kansas [24] and CDC [23] case definitions of Gulf War Illness are illustrated schematically in Figure 1. Symptom domains and constituent individual symptoms are specified for the two case definitions, as well as the exclusionary criteria utilized in the Kansas case definition [54]. [24] and CDC [23] case definitions of Gulf War Illness.…”

Section: Kansas Definitionmentioning

confidence: 99%

Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990–1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006

et al. 2021

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Background: Approximately 697,000 members of the U.S. Armed Forces were deployed to the Persian Gulf in support of the 1990–1991 Persian Gulf War (GW). Subsequently, many deployed and some non-deployed veterans developed a chronic multi-symptom illness, now named Gulf War Illness (GWI). This manuscript outlines the methods and rationale for studying the genomics of GWI within the Million Veteran Program (MVP), a VA-based national research program that has linked medical records, surveys, and genomic data, enabling genome-wide association studies (GWASs). Methods: MVP participants who served in the military during the GW era were contacted by mail and invited to participate in the GWI study. A structured health questionnaire, based on a previously tested instrument, was also included in the mailing. Data on deployment locations and exposures, symptoms associated with GWI, clinical diagnoses, personal habits, and health care utilization were collected. Self-reported data will be augmented with chart reviews and structured international classification of disease codes, to classify participants by GWI case status. We will develop a phenotyping algorithm, based on two commonly used case definitions, to determine GWI status, and then conduct a nested case-control GWAS. Genetic variants associated with GWI will be investigated, and gene–gene and gene–environment interactions studied. The genetic overlap of GWI with, and causative mechanisms linking this illness to, other health conditions and the effects of genomic regulatory mechanisms on GWI risk will also be explored. Conclusions: The proposed initial GWAS described in this report will investigate the genomic underpinnings of GWI with a large sample size and state-of-the-art genomic analyses and phenotyping. The data generated will provide a rich and expansive foundation on which to build additional analyses.

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“…Gulf War veterans began reporting chronic systemic symptoms almost immediately after returning from deployment to the Gulf in support of the 1990–1991 Gulf War [ 1 , 2 , 3 , 4 ]. These symptoms have only increased, in both severity and frequency, over the past 30 years, and have been defined as Gulf War illness (GWI) [ 1 , 5 , 6 , 7 , 8 , 9 , 10 ]. The 2016 Institute of Medicine (IOM) report on GWI indicated great heterogeneity in the expression of GWI across the veteran population, suggesting heterogeneity in genetic susceptibility, environmental exposures, and/or their interactions [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Gene–Toxicant Interactions in Gulf War Illness: Differential Effects of the PON1 Genotype

et al. 2021

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About 25–35% of United States veterans who fought in the 1990–1991 Gulf War report several moderate or severe chronic systemic symptoms, defined as Gulf War illness (GWI). Thirty years later, there is little consensus on the causes or biological underpinnings of GWI. The Gulf War Era Cohort and Biorepository (GWECB) was designed to investigate genetic and environmental associations with GWI and consists of 1343 veterans. We investigate candidate gene–toxicant interactions that may be associated with GWI based on prior associations found in human and animal model studies, focusing on SNPs in or near ACHE, BCHE, and PON1 genes to replicate results from prior studies. SOD1 was also considered as a candidate gene. CDC Severe GWI, the primary outcome, was observed in 26% of the 810 deployed veterans included in this study. The interaction between the candidate SNP rs662 and pyridostigmine bromide (PB) pills was found to be associated with CDC Severe GWI. Interactions between PB pill exposure and rs3917545, rs3917550, and rs2299255, all in high linkage disequilibrium in PON1, were also associated with respiratory symptoms. These SNPs could point toward biological pathways through which GWI may develop, which could lead to biomarkers to detect GWI or to better treatment options for veterans with GWI.

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Gulf War illness in the Gulf War Era Cohort and Biorepository: The Kansas and Centers for Disease Control definitions

Cited by 19 publications

References 21 publications

Brain–Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990–1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study

Brain–Immune Interactions as the Basis of Gulf War Illness: Clinical Assessment and Deployment Profile of 1990–1991 Gulf War Veterans in the Gulf War Illness Consortium (GWIC) Multisite Case-Control Study

Genomics of Gulf War Illness in U.S. Veterans Who Served during the 1990–1991 Persian Gulf War: Methods and Rationale for Veterans Affairs Cooperative Study #2006

Gene–Toxicant Interactions in Gulf War Illness: Differential Effects of the PON1 Genotype

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