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.

项目总结： 唐氏综合征(DS)的个体，自相矛盾地倾向于某些自身免疫状况，包括 乳糜泻，但免于其他疾病，如实体恶性肿瘤。更高价值的机制 DS患者中乳糜泻的患病率尚不清楚。未诊断和未治疗的乳糜泻损害 营养不良会对骨骼健康、生育能力、癌症风险、生长发育、心理健康和死亡率产生终生影响。 乳糜泻的体征和症状可能在DS人群中被掩盖，并坚持目前唯一的 治疗，严格的无麸质饮食，是困难的。这项提案利用了由Include资助的人类三联体 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 DS的乳糜泻征象。长期目标是利用泛经济学数据来获得更好的基本面 了解患有和不患有DS的患者中乳糜泻的发病机制和潜在的生物标志物。这个 中心假设是，在DS患者中存在一种新的泛组学特征，用于治疗乳糜泻。这 假设将通过三个具体的研究目的进行检验：1)比较那些具有 2)收集儿童蛋白质组和代谢组学资料 在没有DS和有和没有乳糜泻的情况下确定乳糜泻的相同分子特征 在无DS的患者中保守。3)探讨遗传风险等位基因对DS患者乳糜泻的影响。这 提案还支持职业发展目标，旨在培养独立所需的技能 乳糜泻和DS个体化医学的研究经费。这项计划将为实习生做好准备 遵循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 管理一个研究团队3)学习生物标记物开发的应用4)为职业独立做准备。 该方法具有创新性，因为它使用了针对多组学数据的创新数据分析技术，以获得 对DS中的乳糜泻有更深的认识。拟议的研究具有重要意义，因为理解 乳糜泻的分子标记可能使未来发展改进的诊断、治疗、 以及对DS患者和普通人群的预防策略。