Integrating genomics and metabolomics data to identify molecular characteristics of Gulf War Veterans' illnesses

海湾战争病是一种慢性、衰弱的疾病，由第一次海湾战争的退伍军人所患。病人 患有GWI的患者通常会受到多年的医疗不确定性的影响，因为他们经历了 诊所试图诊断并最终治疗他们的慢性症状，如果可能的话。使这项医疗工作复杂化 旅程是指缺乏可用于诊断病情的生物标志物，这可能会提供线索 关于治疗和病因学。最近对GWI中生物标记物证据的审查得出结论： 都不是GWI的有效生物标记物。生物标志物的缺乏伴随着治疗的缺乏。 演示了在大量退伍军人中工作。流行病学研究已经成功地发现了 通过海湾大部队的发展，与在海湾战争中服役有共同接触的协会 退伍军人。在少数海湾战争退伍军人中进行的生物标记物研究已经确定了要测试的生物标记物。 其中最有成果的是代谢组学的研究，即对血液中所有小分子或 由能够检测到极少量代谢物的专门仪器测量的组织，然后 将它们与已知化合物进行比较。我们将测试一套全面的代谢物 代谢代谢组学平台涵盖海湾战争中1000多名退伍军人的60多条代谢途径 ERA队列和生物库(GWECB)，由退伍军人事务部收集并提供给研究人员 研究和发展海湾战争计划。代谢组学数据集将连接来自其他分析的数据 GWECB旨在审问其他生物系统。全基因组基因分型测试如何高达100万 基因组中的基因变异导致患有海湾战争疾病的退伍军人与那些 没有。同样，全基因组的表观遗传学分析测试了多达80万个DNA修改如何做出贡献 基因组中不同水平的基因活性。将这三项现代生物医学技术 一起提供了一个关于个体生理差异的全面视图。在合并这些数据时 我们希望找出区别第一次世界大战退伍军人的生物学途径，并建议治疗和生物标志物。 我们还将分析这些组合数据集，以测试构成GWI的较小症状群 可以识别与我们发现的路径相关的GWI的特定亚型。这些数据将返回到 GWECB数据存储库，以便为海湾战争研究社区提供更多信息 研究。

Gulf War Illness (GWI) is a chronic, debilitating illness suffered by Veterans of the first Gulf War. Patients suffering from GWI are often subject to years of medical uncertainty as they make their way through multiple clinics to try to diagnose and ultimately treat their chronic symptoms, if possible. Complicating this medical journey is the absence of biomarkers that can be used to diagnose the conditions and that might provide clues as to treatments and etiology. A recent review of the evidence for biomarkers in GWI concluded that there were no validated biomarkers for GWI. The lack of biomarkers is accompanied by a lack of treatments demonstrated to work in a large number of Veterans. Epidemiologic studies have been successful in identifying associations with exposures common to serving in the Gulf War through development of large cohorts of Gulf War Veterans. Biomarker studies in small numbers of Gulf War Veterans have identified biomarkers for testing. Among the most fruitful of these are studies of metabolomics, the analysis of all small molecules in blood or tissue measured by specialized instruments capable of detecting very small quantities of metabolites and then comparing them to known compounds. We will test a comprehensive set of metabolites assayed by the Metabolon metabolomics platform covering over 60 metabolic pathways in over 1000 Veterans in the Gulf War Era Cohort and Biorepository (GWECB), collected and made available to researchers by the VA Office of Research and Development Gulf War Program. The metabolomics dataset will join data from other assays in GWECB designed to interrogate other biological systems. Genome-wide genotyping tests how up to 1 million genetic variants across the genome contribute to differences in Veterans with Gulf War Illness versus those without. Likewise, genome-wide epigenetic assays test how up to 800,000 DNA modifications contribute different levels of activity of genes across the genome. Putting these three modern biomedical technologies together provides a comprehensive view of physiological differences in individuals. In combining these data we hope to identify biological pathways that distinguish GWI Veterans and suggest treatments and biomarkers. We also will analyze these combined datasets to test whether smaller clusters of symptoms that make up GWI can identify specific subtypes of GWI related to the pathways we find. These data will be returned to the GWECB data repository so that it can be made available to the Gulf War research community for additional research.