Epigenetic Mediation of Genetic Effects in Childhood Asthma
Principal Investigator: Hong Ji, PhD
Asthma is a common disease in pediatric population with contributions from both genetics and environment exposures. This disease disproportionally affects the inner city African American children, due to genetic susceptibility and more frequent exposure to pollution. DNA methylation (DNAm) is the modification of cytosine that regulated gene expression without changing the primary DNA sequence. This epigenetic modification can be determined by both genetic variations (e.g. SNPs located at CpG methylation sites named meSNPs) and environmental exposures.
Our recent studies in a sibling cohort (Exposure sibling study) identified novel DNAm variation associated with asthma and we further replicated some of them in a subpopulation from the Greater Cincinnati Pediatric Clinic Repository. Interestingly, around half of these DNAm variations are associated with meSNPs. Therefore we propose to test the hypothesis that meSNPs contribute to asthma through altering local DNAm. Once completed, proposed research will uncover novel genetic variation associated with asthma and will provide a functional mechanism explaining their contribution to asthma development. Since DNAm is also responsive to environment exposures, the proposal will lead to a continuum of innovative research studying the interplay between individual’s genetic background and environment exposure in childhood asthma. With the fast developing genome and epigenome-targeting technologies, our research may lead to development of new and targeted asthma therapies.