Late Breaking Abstract - Associations between a COPD genetic risk score and lung structure on computed tomography (CT): SPIROMICS

Background: The extent to which genetic risk of COPD is mediated by variation in lung structure remains unknown. Aims: To determine whether a recently developed genetic risk score for lung function (GRS; Wain LV et al, Nat Genet 2017; 49(3):416-425) is associated with CT lung structure. Methods: In SPIROMICS, a cohort of COPD subjects and at-risk smokers (≥20 pack-years), a weighted GRS was calculated from 83 of 95 single nucleotide polymorphisms genotyped or imputed across 3 race/ethnic groups. Post-bronchodilator spirometry and CT scan measures (via Apollo/VIDA) of lung density, spatially-matched airway dimensions, and small airway counts (generations 6-9) were evaluated in models adjusted for age, age-squared, sex, height, BMI, principal components, smoking status, pack-years, CT model and voxel size. Results: Among 2,579 participants (average age 63 years, 53% male, 76% non-Hispanic White, 18% African-American, 6% Asian, 37% current smokers, median 44 pack-years, 63% with COPD), higher GRS was associated with lower FEV1 and FEV1/FVC, and the highest GRS quintile was associated with doubling of risk for moderate-to-severe COPD (p Conclusions: Variation in lung structure, whether developmental or acquired, is an important mediator of the genetic risk factors underlying COPD.