BMI-related Genetic Factors and COPD Imaging Phenotypes

Background: While low body mass index (BMI) is associated with emphysema and obesity is associated with airway disease in chronic obstructive pulmonary disease (COPD), the underlying mechanisms are unclear. Methods: We aggregated genetic variants from population-based genome-wide association studies to generate a polygenic score of BMI (PGSBMI). We calculated this score for participants from COPD-enriched and community-based cohorts and examined associations with automated quantification and visual interpretation of computed tomographic emphysema and airway wall thickness (AWT). We summarized the results using meta-analysis. Results: In the random-effects meta-analyses combining results of all cohorts (n=16,349), a standard deviation increase of the PGSBMI was associated with less emphysema as quantified by log-transformed percent of low attenuation areas ≤ 950 Hounsfield units (β= -0.062, p<0.0001) and 15th percentile value of lung density histogram (β=2.27, p<0.0001), and increased AWT as quantified by the square root of wall area of a 10-mm lumen perimeter airway (β=0.016, p=0.0006) and mean segmental bronchial wall area percent (β=0.26, p=0.0013). For imaging characteristics assessed by visual interpretation, a higher PGSBMI was associated with reduced emphysema in both COPD-enriched cohorts (OR for a higher severity grade=0.89, p=0.0080) and in the community-based Framingham Heart Study (OR for the presence of emphysema=0.82, p=0.0034), and a higher risk of airway wall thickening in the COPDGene study (OR=1.17, p=0.0023). Conclusions: In individuals with and without COPD, a higher body mass index polygenic risk is associated with both quantitative and visual decreased emphysema and increased AWT, suggesting genetic determinants of BMI affect both emphysema and airway wall thickening.