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

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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)