Interstitial Cystitis in Swedish Twins

描述(由申请人提供)： 这项建议的主要目的是利用一项基于大规模人群的经典双胞胎研究的多变量数据，解决间质性膀胱炎(IC)病因学的一系列关键问题。尽管正在进行研究，IC仍然是一个有争议的实体，原因有两个。首先，案件定义的有效性仍然不确定。很少有数据说明历史上重要的验证者--遗传和/或环境因素在多大程度上导致IC。其次，IC通常伴有一种或多种额外的身体疾病，但共病的原因尚不确定。综上所述，这两组悬而未决的问题极大地加剧了围绕IC的争议。此外，IC以女性为主的现象已经有充分的文献记载，但还没有被很好地理解。 为了解决这些基本问题，我们建议在以人口为基础的瑞典双胞胎登记处(STR)对IC进行一项双胞胎研究。我们建议使用基于网络的筛查工具评估年龄在18-45岁的STR双胞胎队列中的IC。那些没有参加网上评估的人将被提供计算机辅助电话面试。根据以往的经验，我们预计，在这一队列中的50,011人中，75%或37,500人将做出回应。这些独特的数据将被用来解决以下具体目标：(1)估计STR参与者中IC及其主要共病的患病率。评估IC与其他疾病共病的表型模式。(2)通过协和分析和结构方程模型分析了遗传和环境因素对遗传变异的影响。以考察性别对这些影响的影响。(3)使用多变量双生分析来研究IC与其频繁共病情况之间的协变来源；(4)使用病例对照设计(“共生对照”设计)来评估暴露可能推断疾病风险的重要性。

DESCRIPTION (provided by applicant): The overarching purpose of this proposal is to address a set of critical questions about the etiology of interstitial cystitis (IC) using multivariate data from a large population-based classical twin study. Despite ongoing research, IC remains a controversial entity for two critical reasons. First, the validity of the case definition remains uncertain. There are few data that address a historically important validator--the degree to which IC results from genetic and/or environmental factors. Second, IC is often comorbid with one or more additional physical disorders and yet the causes of comorbidity are uncertain. Taken together, these two sets of unanswered questions contribute significantly to the controversies that continue to surround IC. Moreover, the strong female predominance of IC has been amply documented but is not well understood. To address these fundamental issues, we propose to conduct a twin study of IC in the population-based Swedish Twin Registry (STR). We propose to assess IC in the cohort of STR twins aged 18-45 years using a web-based screening instrument. Those not participating in the web-based assessment will be offered a computer assisted telephone interview. Based on previous experience, we anticipate that of the 50,011 individuals in this cohort, 75% or 37,500 will respond. These unique data will be used to address the following Specific Aims: (1) To estimate the prevalence of IC and its key co-morbidities in STR participants. To assess the phenotypic patterns of comorbidity of IC with other disorders. (2) To evaluate the genetic and environmental sources of variation for IC through concordances and structural equation modeling. To examine the effects of gender on these effects. (3) To use multivariate twin analyses to investigate the sources of covariation between IC and its frequently co-morbid conditions and (4) To use case-control designs with external controls and internal controls ("co-twin control" design) to evaluate the importance of exposures which may infer risk for disease.