Genetic epidemiology of irritable bowel syndrome (IBS)

描述（由申请人提供）： Yuri Ann Saito的长期研究目标是了解功能性胃肠道疾病的病理生理学，以便为这种影响10- 20%人口的常见疾病找到有效的治疗方法。她认为，这可以通过使用先进的流行病学方法部分实现。K23指导的以患者为导向的研究职业发展奖将提供一个极好的机会，以获得在功能性胃肠道疾病中进行高质量流行病学和遗传流行病学研究的经验。拟议的研究计划旨在扩大我们对肠易激综合征（IBS）在家庭中聚集的原因的基本理解，并评估导致IBS的环境和可能的遗传因素。一个结合病例对照和家庭研究的建议，问卷数据将收集从500个临床为基础的IBS患者，500个临床为基础的控制，大约5000个一级亲属。本研究的目的是回答IBS是否真的在家庭中聚集，家族性IBS的特征是什么，以及IBS在家庭中的传播是否遵循遗传模式。因此，本研究由3个互补部分组成：家族聚集性研究，分类回归树（CART）分析，以确定家族性IBS的临床和流行病学特征，以及复杂的分离分析，以确定是否有IBS的主要基因的证据。这项研究的意义在于，它将提供有意义的科学数据，证明未来的遗传学研究是合理的，包括更广泛的基于生物标志物的研究，寻找候选基因。该研究还将深入了解导致IBS及其可变表现的非遗传因素。这个职业奖将建立在她以前的经验，使用基于调查的数据来研究诊所的病人和社区和她的MPH。这将使她能够通过课程、参加研讨会以及通过项目本身在一个拥有丰富临床和流行病学研究资源的机构获得遗传流行病学、统计遗传学和遗传学方面的培训。额外的培训和从这个研究职业发展奖产生的数据将确保她将推进她的学术生涯，成功地竞争独立的同行评审的资金，并作出重大的科学贡献，这种和其他胃肠道疾病的理解。

DESCRIPTION (provided by applicant): Yuri Ann Saito's long-term research objective is to understand the pathophysiology of functional gastrointestinal disorders so that effective treatments may be found for this common disorder that affects 10- 20% of the population. She believes that this can be achieved in part through the use of advanced epidemiological methods. The K23 Mentored Patient-Oriented Research Career Development Award would provide an excellent opportunity to gain experience in conducting high-quality epidemiological and genetic epidemiological research in functional gastrointestinal diseases. The proposed research plan is targeted toward expanding our basic understanding of why irritable bowel syndrome (IBS) appears to cluster in families, and to evaluate the environmental and possible genetic factors contributing to IBS. A combined case-control and family study is proposed where questionnaire data will be collected from 500 clinic-based patients with IBS, 500 clinic-based controls, and approximately 5000 first-degree relatives. The aims of this study are geared to answer whether IBS truly aggregates in families, what are the characteristics of familial IBS, and whether IBS transmission in families follows a genetic pattern. Thus, this study composed of 3 complementary sections: a familial aggregation study, classification regression tree (CART) analysis to identify clinical and epidemiological features of familial IBS, and complex segregation analysis to determine whether there is evidence of a major gene for IBS. This study's significance is that it will provide meaningful scientific data that would justify future genetic studies including a more extended biospecimen-based study with a search for candidate genes. The study will also provide insight into the non-genetic factors that lead to IBS and its variable manifestations. This career award would build upon her previous experience using survey-based data to study clinic patients and the community and her M.P.H. It would allow her to obtain training in genetic epidemiology, statistical genetics, and genetics through coursework, attending seminars, and through the project itself at an institution rich in clinical and epidemiological research resources. The additional training and the data generated from this research career development award would ensure that she would advance her academic career, successfully compete for independent peer-reviewed funding, and make significant scientific contributions to the understanding of this and other gastrointestinal disorders.