Overview (S-000086)
Chronic Obstructive Pulmonary Disease (COPD) is a common inflammatory lung disease that is characterized by persistent respiratory symptoms and progressive airflow limitation. Because COPD is the consequence of the combined effects of environmental factors and genetic susceptibility, mechanisms that link gene and environment may hold clues to its pathogenesis and its outcomes. Epigenetic modifications such as DNA methylation where a methyl group can be added to or removed from a cytosine base located next to a guanine base (CpG site) represent dynamic mechanisms by which environmental factors can influence gene expression and subsequent lung injury. These modifications are also highly involved in the aging process,1,2 yielding multiple methylation clocks that have demonstrated impressive sensitivity for capturing accelerated aging.3–6 DNA methylation is thus a powerful tool to study gene regulation and aging in chronic lung disease. Our group has previously determined that methylation age acceleration is associated with acute exacerbations, quality of life, and mortality in COPD.7,8 Nonetheless, small sample sizes and cross-sectional measurements limit our understanding of the role of methylation in long-term health outcomes in COPD. The CanCOLD cohort has both the size and phenotypic depth to demonstrate the power of DNA methylation in blood samples as a prognostic biomarker in COPD and as a window into candidate genes whose epigenetic modifications may contribute to disease pathogenesis. Specifically, we propose a two-stage approach: first, to combine existing DNA methylation data already generated from the CanCOLD cohort by UBC (Leung) and Queen’s University (Duan) (total n=100) to explore preliminary relationships between DNA methylation and health outcomes in COPD and second, to use these preliminary results to support a CIHR grant application which can fund the completion of DNA methylation in blood samples from all CanCOLD participants. If successful, this grant will fund a study that can identify aging biomarkers to predict important clinical outcomes in the CanCOLD cohort and also through an integrative ‘omics approach with already available genotyping data, identify candidate genes associated with COPD. We believe this study will have major novelty and impact given CanCOLD’s ability to capture early and milder forms of disease often overlooked by international COPD cohorts and the wealth of longitudinal phenotyping available.
Contact Details
- Name
- Dr Janice M. Leung
- Institution
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Centre for Heart Lung Innovation (HLI), University of British Columbia