Ancestry-Environmental Exposure Interactions and Asthma Risk in Admixed Population

项目总结/文摘

Project Summary/Abstract The burden of asthma is disproportionately high among minority children, in particular children of African descent. African American (AA) children are four times more likely to be hospitalized and seven times more likely to die from asthma than non-AAs. Recent studies have identified genetic and environmental exposure factors that contribute to asthma risk; however, the extent to which these factors interact to explain a person’s risk to asthma remains largely unknown. Our long-term goal is to develop a program of study that would lead to an in-depth understanding of the complex interplay between genetic and non-genetic causes of asthma among AA children, and establish the utility of this information to reduce and predict asthma risk in children. The objective of this study is to investigate the interactions between genetic ancestry and environmental exposure risk factors contributing to asthma risk in AA children using a well characterized cohort with banked DNA samples, environmental exposure and clinical data as well as ancestry informative markers. We hypothesize that genetic variants with large allele frequency differences and variation in environmental exposures between African and European ancestry may be partly responsible for the current difference in asthma risk in African American admixed ancestry. Moreover, ancestry and environmental exposure may jointly influence the variation and development of asthma. Two Specific Aims are proposed to test our hypothesis and achieve our proposed plan: Aim 1) Determine local and global genetic ancestry in AA asthmatic children using ancestry informative markers (AIMs); and Aim 2) Identify interactions between local ancestry and environmental exposure risk factors. The proposed study is highly significant (it addresses a major public health issue given the high burden of asthma among minority children) and highly innovative (it dissects the genetic and non- genetic causes of asthma disparities using ancestry mapping). Ultimately, this research may provide the link and insight between asthma and genetic and non-genetic factors and has potential avenues for intervention. Success in this R03 application will provide key knowledge and data to apply for fundable R01 grant application related to racial disparities in childhood asthma. We therefore believe that this pilot study along with future studies will uncover fundamental information about whether genetic factors and selected environmental exposure factors as well as their interactions can affect asthma risk and prediction, thereby reducing the burden of asthma on patients and their families and improving their quality of life. 1