BMI-related Genetic Factors and COPD Imaging Phenotypes

Abstract 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 (PGS BMI ). 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 PGS BMI 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 15 th 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 PGS BMI 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.