Body Mass Index-related genetic factors and COPD imaging phenotypes

RATIONALE: 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. OBJECTIVES: To examine the association between BMI-related genetic variants and emphysema and airway disease imaging phenotypes. METHODS: We aggregated genetic variants from population-based genome-wide association studies to generate a polygenic score of BMI (PGSBMI). We examined associations of the PGSBMI with automated quantification and visual interpretation of computed tomographic emphysema and airway wall thickness (AWT) in COPD-enriched and community-based cohorts. We summarized the results using meta-analysis. MEASUREMENTS AND MAIN RESULTS: In the 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 < .0001) and 15th percentile value of lung density histogram (β = 2.27, P < .0001), and increased AWT as quantified by the square root of wall area of a 10-mm lumen perimeter airway (β = 0.016, P = .0006) and mean segmental bronchial wall area percent (β = 0.26, P = .0013). For imaging characteristics assessed by visual interpretation, a higher PGSBMI was associated with reduced emphysema in both COPD-enriched cohorts (odds ratio [OR] for a higher severity grade = 0.89, P = .0080) and in the community-based Framingham Heart Study (OR for the presence of emphysema = 0.82, P = .0034), and a higher risk of airway wall thickening in the COPDGene study (OR = 1.17, P = .0023). CONCLUSIONS: In individuals with and without COPD, a higher BMI 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.