Celiac disease signatures in Down syndrome (KL2 Admin Suppl)

唐氏综合症的乳糜泻特征（KL2 Admin Suppl）

• 批准号: 10117961
• 负责人: ELLEN L BURNHAM
• 金额: $ 14.04万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10117961
• 关键词: Adherence; Autoimmune Process; Celiac Disease; Child; Cohort Studies; Data; Data Analyses; Development; Diagnostic; Diet; Down Syndrome; Early Diagnosis; Enrollment; Fertility; Funding; Future; General Population; Genetic Risk; Gluten; Goals; Growth; High Prevalence; Human; Impairment; Individual; Knowledge; Learning; Malignant Neoplasms; Masks; Mental Health; Molecular Profiling; Monitor; Multiomic Data; Pathogenesis; Population; Prevention strategy; Proteomics; Research; Risk; Signs and Symptoms; Solid; Techniques; Testing; Therapeutic; biomarker development; bone health; cancer risk; career; career development; disease diagnosis; improved; innovation; metabolomics; mortality; novel; nutrition; personalized medicine; potential biomarker; risk variant; skills

Project Summary: Individuals with Down syndrome (DS), are paradoxically predisposed to certain autoimmune conditions including celiac disease, but spared from other conditions such as solid malignancies. The mechanism for the higher prevalence of celiac disease in DS remains unknown. Undiagnosed and untreated celiac disease impairs nutrition and can have lifelong impacts on bone health, fertility, cancer risk, growth, mental health, and mortality. Signs and symptoms of celiac disease may be masked in the DS population and adherence to the only current treatment, a strict gluten-free diet, is difficult. This proposal leverages the INCLUDE-funded Human Trisome Project (HTP), a large cohort study of individuals with DS using pan-omics approaches, to study the molecular signatures of celiac disease in DS. The long term goal is to utilize pan-omics data to gain a better fundamental understanding of the pathogenesis and potential biomarkers of celiac disease in those with and without DS. The central hypothesis is that there is a novel pan-omics signature for celiac disease in those with DS. This hypothesis will be tested with three specific research aims: 1) Compare the molecular signature of those with DS enrolled in the HTP with and without celiac disease 2) Collect proteomics and metabolomics from children without DS and with and without celiac disease to determine if the same molecular signatures of celiac disease are conserved in those without DS 3) Explore the impact of genetic risk alleles on celiac disease in DS. This proposal also supports career development aims geared to building the necessary skills for independent research funding in celiac disease and DS personalized medicine. This plan will prepare the trainee with the following four specific career development aims: 1) Develop skills needed to analyze multi-omics data 2) Learn to manage a research team 3) Learn applications of biomarker development 4) Prepare for career independence. The approach is innovative because it uses innovative data analysis techniques for multi-omics data to gain a deeper understanding of celiac disease in DS. The proposed research is significant because understanding the molecular signatures of celiac disease may enable the future development of improved diagnostic, therapeutic, and preventative strategies in those with DS and for the general population.

项目摘要： 唐氏综合征（DS）患者自相矛盾地易患某些自身免疫性疾病，包括 乳糜泻，但免于其他条件，如固体恶性肿瘤。更高层次的机制 DS中乳糜泻的患病率仍然未知。未经诊断和治疗的乳糜泻损害 它可能对骨骼健康、生育力、癌症风险、生长、心理健康和死亡率产生终身影响。 乳糜泻的体征和症状可能在DS人群中被掩盖，并且坚持目前唯一的治疗方案。 严格的无麸质饮食是很困难的。该提案利用了INCLUDE资助的人类三体 项目（HTP），一项使用泛组学方法对DS患者进行的大型队列研究，以研究分子生物学。 乳糜泻的症状长期目标是利用泛经济学数据获得更好的基本面 了解乳糜泻的发病机制和潜在的生物标志物在那些有和没有DS。的 中心假设是，DS患者的乳糜泻存在一种新的泛组学特征。这 假设将通过三个具体的研究目标进行测试：1）比较那些具有以下特征的分子特征： 入选HTP的DS伴和不伴乳糜泻2）收集儿童的蛋白质组学和代谢组学 没有DS和有和没有乳糜泻，以确定是否有相同的乳糜泻分子特征 在没有DS的那些中是保守的3）探索遗传风险等位基因对DS中乳糜泻的影响。这 该提案还支持职业发展目标，旨在培养独立工作者的必要技能。 乳糜泻和DS个性化医疗的研究资金。该计划将为受训者提供 以下四个具体的职业发展目标：1）培养分析多组学数据所需的技能2）学习 管理研究团队3）学习生物标志物开发的应用4）为职业独立做好准备。 这种方法是创新的，因为它使用了创新的数据分析技术，多组学数据，以获得一个 更深入地了解DS中的乳糜泻。这项研究的意义在于， 乳糜泻的分子特征可以使将来能够开发改进的诊断，治疗， 和预防策略，在那些与DS和一般人群。