Role of Prenatal Factors and Gene-Environment Interactions in Recurrent Wheezing

描述（由申请人提供）：这个职业发展奖将促进库马尔博士发展成为一个独立的研究人员在遗传流行病学领域的哮喘和喘息混合少数民族人口。培训将在一个独特而丰富的环境中进行，并由王晓斌博士，罗伯特·施莱默博士和卡罗尔·奥伯博士指导。外部顾问包括James热尔恩博士和Esteban Burchard博士。培训将包括：遗传流行病学的教学教育;在候选基因和SNP选择，基因分型，遗传数据采集和分析的实践经验; GxE研究的理论和统计方法的理解;和发展在内城纵向队列研究的专业知识。这些教育目标将与该项目的具体目标并行实现，具体如下：目标1：我们将评估早产和绒毛膜炎与波士顿出生队列中早期喘息的后续发展之间的关联。目标二：我们将进行巢式病例对照研究，以评估目标1中观察到的关联是否可以通过候选基因的个体变体进一步修改，调整重要协变量，多重比较和人群分层后。我们将对以下几组候选基因的常见基因多态性进行基因分型：1.参与绒毛膜炎反应途径的基因，包括炎症反应途径和肺损伤途径的重塑/调节。2.免疫调节天然免疫候选基因。该项目的长期科学目标是评估产前因素与儿童早期喘息复发差异的相关程度，以及这些相关性是否因遗传变异而改变。这一未被调查的领域具有公共卫生意义，因为非裔美国人的内城人口有更高的喘息和哮喘发病率，传统的危险因素不能解释这些差异。然而，早产儿和特别是绒毛膜炎是差异分布沿着这些相同的线，并有一些生物学原理的关联，这两个共病流行病。阐明这些关系可能会导致更好地了解差异和预防喘息的发病率。 (End摘要）

DESCRIPTION (provided by applicant): This career development award will foster Dr. Kumar's development into an independent investigator in the area of genetic epidemiology of asthma and wheezing in admixed minority populations. Training will occur in a uniquely rich environment with mentoring from Dr. Xiaobin Wang, Dr. Robert Schleimer, and Dr. Carole Ober. External advisors include Dr. James Gern and Dr. Esteban Burchard. Training will include: didactic education in genetic epidemiology; practical experience in candidate gene and SNP selection, genotyping, genetic data acquisition and analysis; understanding of theoretical and statistical methods of GxE research; and developing expertise in inner city longitudinal cohort studies. These educational goals will be achieved in parallel to the project's specific aims as follows: Aim 1: We will evaluate the association of prematurity and chorioamnionitis with the subsequent development of early life wheezing in the Boston Birth Cohort. Aim 2: We will carry out a nested case control study to evaluate whether the associations observed in Aim 1 can be further modified by individual variants of candidate genes, after with adjustment for important covariates, multiple comparisons and population stratification. We will genotype common gene polymorphisms of the following groups of candidate genes: 1. Genes which are involved in the pathways of response to chorioamnionitis, including inflammatory response pathways and remodeling/modulation of lung injury pathways. 2. Immunoregulatory Innate Immunity Candidate Genes. The long term scientific goal of the project is to evaluate the extent to which prenatal factors are associated with disparities in recurrent early childhood wheezing, and whether these associations are modified by genetic variation. This under investigated area is of public health significance because African American inner city populations have much higher rates of wheezing and asthma ,and traditional risk factors do not explain these disparities. However, prematurity and specifically chorioamnionitis are differentially distributed along these same lines, and there is some biological rationale for the association of these two co-morbid epidemics. Elucidating these relationships may lead to improved understanding of disparities and prevention of wheezing morbidity. (End of Abstract)