Visual Assessment of Chest Computed Tomographic Images IsIndependently Useful for Genetic Association Analysis in Studies of ChronicObstructive Pulmonary Disease

摘要

>Rationale: Automated analysis of computed tomographic (CT) lung images for epidemiologic and genetic association studies is increasingly common, but little is known about the utility of visual versus semiautomated emphysema and airway assessments for genetic association studies.>Objectives: Assess the relative utility of visual versus semiautomated emphysema and airway assessments for genetic association studies.>Methods: A standardized inspection protocol was used to visually assess chest CT images for 1,540 non-Hispanic white subjects within the COPDGene Study for the presence and severity of radiographic features representing airway wall thickness and emphysema. A genome-wide association study (GWAS) was performed, and two sets of candidate single-nucleotide polymorphisms with a higher prior likelihood of association were specified a priori for separate analysis. For each visual CT examination feature, a corresponding semiautomated CT feature(s) was identified for comparison in the same subjects.>Measurements and Main Results: GWAS for visual features of chest CT scans identified a genome-wide significant association with visual emphysema at the 15q25 locus (P = 6.3e⁻⁹). In thea priori–specified set of 19 previously identifiedGWAS loci, 7 and 8 loci were associated with airway measures or emphysemameasures, respectively. In the a priori–specifiedcandidate gene set, 13 of 196 candidate genes harbored a nearbysingle-nucleotide polymorphism significantly associated with an emphysemaphenotype. Visual CT examination associations were robust to adjustment forsemiautomated correlates in many cases.>Conclusions: Standardized visual assessments of emphysema and airwaydisease are significantly associated with genetic loci previously associatedwith chronic obstructive pulmonary disease susceptibility or semiautomated CTexamination phenotypes in GWAS. Visual CT measures of emphysema and airwaysdisease offer independent information for genetic association studies inrelation to standard semiautomated measures.