Visual Assessment of Chest Computed Tomographic Images Is Independently Useful for Genetic Association Analysis in Studies of Chronic Obstructive Pulmonary Disease.

rationaleAutomated 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.

objectivesAssess the relative utility of visual versus semiautomated emphysema and airway assessments for genetic association studies.

methodsA 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

resultsGWAS for visual features of chest CT scans identified a genome-wide significant association with visual emphysema at the 15q25 locus (P = 6.3e

conclusionsStandardized visual assessments of emphysema and airway disease are significantly associated with genetic loci previously associated with chronic obstructive pulmonary disease susceptibility or semiautomated CT examination phenotypes in GWAS. Visual CT measures of emphysema and airways disease offer independent information for genetic association studies in relation to standard semiautomated measures.