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.

项目概要： 矛盾的是，患有唐氏综合症 (DS) 的人容易患某些自身免疫性疾病，包括 乳糜泻，但不受其他疾病的影响，例如实体恶性肿瘤。上级机制 DS 中乳糜泻的患病率仍不清楚。未经诊断和未经治疗的乳糜泻会损害 营养，并对骨骼健康、生育能力、癌症风险、生长、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，并且坚持目前唯一的治疗方法 严格的无麸质饮食治疗是很困难的。该提案利用了 INCLUDE 资助的人类三体 项目 (HTP) 是一项使用泛组学方法对 DS 个体进行的大型队列研究，旨在研究分子 DS 中乳糜泻的特征。长期目标是利用泛组学数据获得更好的基本面 了解患有和不患有 DS 的乳糜泻患者的发病机制和潜在生物标志物。这 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研究目标进行检验：1）比较那些具有以下特征的分子特征： DS 参加 HTP 时患有或不患有乳糜泻 2) 收集儿童的蛋白质组学和代谢组学 没有 DS 以及有或没有乳糜泻，以确定乳糜泻的分子特征是否相同 在没有 DS 的患者中是保守的 3) 探索遗传风险等位基因对 DS 乳糜泻的影响。这 提案还支持职业发展目标，旨在培养独立的必要技能 乳糜泻和 DS 个性化医疗的研究经费。该计划将使受训者做好准备 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。 该方法具有创新性，因为它使用创新的多组学数据分析技术来获得 对 DS 乳糜泻有更深入的了解。拟议的研究意义重大，因为了解 乳糜泻的分子特征可能有助于未来改进诊断、治疗、 DS 患者和普通人群的预防策略。