Body Mass Index-related genetic factors and COPD imaging phenotypes
Year: 2026
Type: article
Abstract: 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.
Authors: Jingzhou Zhang, Matthew Moll, Catherine L Debban, Brian D Hobbs, Heena Rijhwani, George R Washko, Bartolome R Celli, Edwin K Silverman, Per Bakke, Elizabeth C Oelsner, R Graham Barr, Alvar Agustí, Rosa Faner, Guy G Bruselle, Stephen M Humphries, David A Lynch, Josée Dupuis, Ani W Manichaikul, George T O’Connor, Michael H Cho
Institutions: Boston University, Brigham and Women's Hospital, Harvard University, VA Boston Healthcare System, University of Virginia, University of Bergen, Columbia University Irving Medical Center, Columbia University, Hospital Clínic de Barcelona, Consorci Institut D'Investigacions Biomediques August Pi I Sunyer, Universitat de Barcelona, Ghent University Hospital, National Jewish Health, McGill University, Framingham Heart Study
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Genetic and Functional Dissection of a Cluster of COPD GWAS Signals on Chromosome 4q, G4976486911, G5380350839, Identifying Protein-Protein Network Interactions between COPD Susceptibility Genes, G9000002950, G9000071188, G9000081360, G9000219965, COPD Susceptibility, Heterogeneity, and Progression: Proteomics and Genetics, Multi-omic Risk Prediction of Chronic Obstructive Pulmonary Disease in European- and African-Ancestry Populations, G91397193
OpenAlex ID: W7130846413