DSP variants may be associated with longitudinal change in quantitative emphysema

Background Emphysema, characterized by lung destruction, is a key component of Chronic Obstructive Pulmonary Disease (COPD) and is associated with increased morbidity and mortality. Genome-wide association studies (GWAS) have identified multiple genetic factors associated with cross-sectional measures of quantitative emphysema, but the genetic determinants of longitudinal change in quantitative measures of emphysema remain largely unknown. Our study aims to identify genetic variants associated with longitudinal change in quantitative emphysema measured by computed tomography (CT) imaging. Methods We included current and ex-smokers from two longitudinal cohorts: COPDGene, a study of Non-Hispanic Whites (NHW) and African Americans (AA), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). We calculated annual change in two quantitative measures of emphysema based on chest CT imaging: percent low attenuation area (≤ − 950HU) (%LAA-950) and adjusted lung density (ALD). We conducted GWAS, separately in 3030 NHW and 1158 AA from COPDGene and 1397 Whites from ECLIPSE. We further explored effects of 360 previously reported variants and a lung function based polygenic risk score on annual change in quantitative emphysema. Results In the genome-wide association analysis, no variants achieved genome-wide significance (P