Genetic & epidemiologic cohort study of asthma & allergy

描述(申请人提供)：过敏性哮喘、湿疹、花粉热和食物过敏的发病率和严重程度最近急剧增加，特别是在儿童中；在美国，每四个儿童中就有一个受到影响。这些过敏性疾病的表现是多种多样的，并随着时间的推移而发展。考虑到这种时序变化，在单个时间点对儿童进行评估可能不会得出关于过敏性疾病的准确情况。我们有一个独特的队列，超过1,000名儿童在出生时(-1990年)患有哮喘和过敏，年龄分别为1、2、4和10岁。使用来自这个队列的纵向数据，我们建议识别变态反应性疾病的时间依赖模式，我们称之为过敏轨迹。遗传易感性是导致哮喘和过敏的关键因素，但我们对这些炎症性疾病的易感基因的了解有限。为了更好地了解过敏性哮喘和其他过敏性疾病的机制，我们将从我们的儿童队列中收集DNA样本，研究被认为介导过敏性炎症的候选基因IL4、IL4R、IL13、IL1和IL1RN。我们将使用一种新的方法来进行遗传关联研究，使用过敏轨迹作为表型，而不是依赖于在单个时间点评估的参数。除了遗传易感性，环境暴露被认为影响过敏性疾病的存在和严重程度。然而，基因和环境之间相互作用的性质仍然不清楚。因此，我们将评估选定的候选基因与队列儿童中常见环境暴露之间的基因x环境交互作用。 我们组建了一支经验丰富的多学科研究团队，拥有遗传学、流行病学、临床医学(过敏和免疫学)和生物统计学方面的专业知识。有了这个团队，我们将能够通过扩大哮喘和过敏的流行病学分析，并开始对候选基因进行遗传关联分析，为全面描述儿童队列研究人群奠定坚实的基础。通过确定这一队列中的遗传和环境风险因素，我们将为卫生保健专业人员和父母提供有价值的信息，帮助他们进行管理，将易感儿童的风险降至最低。

DESCRIPTION (provided by applicant): Dramatic increases in the incidence and severity of allergic asthma, eczema, hay fever and food allergy have been seen recently, particularly in children; every fourth child in the U.S. is affected. Manifestations of these allergic diseases are varied and progress over time. Given this chronological variation, the assessment of children at a single time point may not yield an accurate picture of allergic disease. We have a unique cohort of over 1,000 children characterized for asthma and allergy at birth (in 1989-1990) and ages 1, 2, 4, and 10 years. Using longitudinal data from this cohort we propose to identify time-dependent patterns of allergic disorders, which we term allergic trajectories. Genetic predisposition is a key factor underlying asthma and allergy, yet our knowledge of susceptibility genes for these inflammatory disorders is limited. To gain greater understanding of the mechanisms of allergic asthma and other allergies, we will investigate candidate genes thought to mediate allergic inflammation, IL4, IL4R, IL13, IL1 and IL1RN, in DNA samples collected from our cohort of children. We will use a novel approach to perform genetic association studies by using allergic trajectories as phenotypes instead of relying on parameters assessed at a single time point. In addition to genetic susceptibility, environmental exposures are thought to influence both the presence and severity of allergic diseases. However, the nature of the interaction between genes and the environment remains unclear. Thus, we will assess gene x environment interactions between selected candidate genes and common environmental exposures in cohort children. We have assembled a highly experienced multidisciplinary research team with expertise in genetics, epidemiology, clinical medicine (allergy and immunology) and biostatistics. With this team we will be able to build on a strong foundation of a thoroughly characterized childhood cohort study population by expanding the epidemiologic analyses of asthma and allergy, and beginning genetic association analyses of candidate genes. By determining genetic and environmental risk factors in this cohort, we will contribute information valuable to both health care professionals and parents regarding management practices to minimize risks to susceptible children.