Risk factors for asymptomatic diverticulosis

项目摘要 结肠憩室病在美国是一种常见病。憩室病可并发急性 炎症、感染、出血，统称为憩室病。憩室的负担 估计每年要花费40亿美元。这项研究的第一阶段收集了详细的信息， 在600多名接受结肠镜检查的人身上进行了关于憩室的研究。收效 挑战传统智慧。与预期相反的是，增加的胰岛素水平没有保护作用。 纤维、体力活动或定期排便。没有证据表明，慢性炎症， 憩室病患者的结肠。不同种族的结肠憩室分布不同， 黑人的右侧憩室更多。来自其他人的令人信服的证据表明，遗传因素可能是 负责大约一半的风险憩室疾病，但没有相关性 在大量患者中进行研究。拟议的研究建立在基础设施和信息的基础上 已经组装，以解决四个具体目标：1）进行全基因组关联研究的存档 来自624名特征明确的患者的DNA，以确定憩室病的可能遗传决定因素。2)到 评估与憩室病相关的差异基因表达。3)进行有针对性的关联研究 使用从GWAS中鉴定的候选物和存档DNA上的差异基因表达来确认遗传学。 使用来自第二个群体的1824名结肠镜检查患者的储存DNA进行憩室病的决定因素。4)到 在憩室病队列中随访个体，以确定是否存在憩室病， 与慢性胃肠道症状的发展有关。以实验室为基础的目标是 使用已经收集的标本完成。之前描述的GWAS方法将 确定可能导致憩室病的遗传变异。RNAseq将全面比较 与对照相比，憩室病病例的转录组。对以前登记的人进行后续访谈 受试者将评估症状发展。这项研究是创新的，因为它将是第一个大型的 前瞻性队列研究使用结构检查（结肠镜检查）对憩室病病例进行准确分类。 同样，也没有基于结构检查的大型遗传研究。本研究的成功完成 可以为研究和病人护理开辟新的途径。

PROJECT SUMMARY Colonic diverticulosis is a common condition in the United States. Diverticulosis can be complicated by acute inflammation, infection, hemorrhage, collectively termed diverticular disease. The burden of diverticular disease is estimated at $4 billion dollars annually. The first phase of this study collected detailed information about diverticula on more than 600 individuals who underwent screening colonoscopy. The results have challenged conventional wisdom. Contrary to expectation, there was no protective association with increased fiber, physical activity or regular bowel movements. There was no evidence of chronic inflammation in the colons of individuals with diverticulosis. There was a different colonic distribution of diverticula by race, with more right-sided diverticula for blacks. Compelling evidence from others indicates that genetic factors may be responsible for approximately half of the risk for diverticular disease, but there have been no association studies in large numbers of patients. The proposed research builds on the infrastructure and information already assembled to address four specific aims: 1) To perform a genome-wide association study on archived DNA from 624 well-characterized patients to identify possible genetic determinants of diverticulosis. 2) To assess differential gene expression associated with diverticulosis. 3) To perform a targeted association study using candidates identified from GWAS and differential gene expression on archived DNA to confirm genetic determinants of diverticulosis using stored DNA from a second population of 1824 colonoscopy patients. 4) To follow-up individuals in the diverticulosis cohort to determine whether the presence of diverticulosis is associated with the development of chronic gastrointestinal symptoms. The laboratory-based aims will be accomplished using specimens that have already been collected. Previously described GWAS methods will identify genetic variants that may contribute to diverticulosis. RNAseq will comprehensively compare the transcriptomes of diverticulosis cases compared to controls. Follow-up interviews on previously enrolled subjects will evaluate symptom development. The study is innovative because it will be the first large prospective cohort that has used a structural exam (colonoscopy) to accurately classify diverticulosis cases. Similarly, there are no large genetic studies based on structural exams. Successful completion of this study could open new avenues for research and patient care.