Risk factors for asymptomatic diverticulosis

项目总结 结肠憩室病在美国是一种常见的疾病。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 据估计，疾病每年造成40亿美元的损失。这项研究的第一阶段收集了详细的信息 对600多名接受结肠镜检查的人进行了关于憩室的调查。结果是 挑战传统智慧。与预期相反，没有保护性的关联与增加 纤维、体力活动或有规律的排便。没有证据表明慢性炎症在 憩室病患者的结肠。憩室的结肠分布因种族不同而不同， 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 负责大约一半的憩室病的风险，但没有关联 对大量患者进行的研究。拟议的研究建立在基础设施和信息的基础上 已经集合起来以实现四个具体目标：1)对已归档的 从624名特征良好的患者中提取DNA，以确定可能的憩室病遗传决定因素。2)至 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 利用从GWAS中鉴定的候选基因和存档DNA上的差异基因表达来确认遗传 利用1824例结肠镜检查患者中储存的DNA研究憩室病的决定因素。4)至 对憩室病队列中的个体进行随访，以确定憩室病的存在是否 与慢性胃肠道症状的发展有关。基于实验室的目标将是 使用已经收集的标本完成的。前面描述的GWAS方法将 确定可能导致憩室病的基因变异。RNAseq将全面比较 憩室病患者与对照组的转录本比较。对以前录取的学生进行后续面试 受试者将评估症状的发展。这项研究具有创新性，因为它将是第一个 使用结构检查(结肠镜)准确地对憩室病病例进行分类的前瞻性队列研究。 同样，目前还没有基于结构测试的大型遗传学研究。顺利完成这项研究 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.