Projects per year
Epigenome-wide association studies (EWASs) of respiratory function and COPD were performed in peripheral blood samples from the Generation Scotland: Scottish Family Health Study (GS:SFHS) cohort (n = 3781; 274 COPD cases and 2919 controls). In independent COPD incidence data (n = 149), significantly differentially methylated sites (DMSs; p < 3.6 × 10−8) were evaluated for their added predictive power when added to a model including clinical variables, age, sex, height and smoking history using receiver operating characteristic analysis. The Lothian Birth Cohort 1936 (LBC1936) was used to replicate association (n = 895) and prediction (n = 178) results.
We identified 28 respiratory function and/or COPD associated DMSs, which mapped to genes involved in alternative splicing, JAK-STAT signalling, and axon guidance. In prediction analyses, we observed significant improvement in discrimination between COPD cases and controls (p < .05) in independent GS:SFHS (p = .016) and LBC1936 (p = .010) datasets by adding DMSs to a clinical model.
Identification of novel DMSs has provided insight into the molecular mechanisms regulating respiratory function and aided prediction of COPD risk. Further studies are needed to assess the causality and clinical utility of identified associations.
Wellcome Trust Strategic Award 10436/Z/14/Z.
1/09/13 → 31/08/19
- Deanery of Molecular, Genetic and Population Health Sciences - Reader
- Centre for Genomic and Experimental Medicine
- Edinburgh Neuroscience
Person: Academic: Research Active