• Eitan Halper-Stromberg, Michael H Cho, Carla Wilson, Dipti Nevrekar, James D Crapo, George Washko, Raúl San José Estépar, David A Lynch, Edwin K Silverman, Sonia Leach, and Peter J Castaldi.
• 1 Computational Biosciences Program, University of Colorado, Denver, Aurora, Colorado.
• Ann Am Thorac Soc. 2017 Jan 1; 14 (1): 33-40.

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-9). In the a priori-specified set of 19 previously identified GWAS loci, 7 and 8 loci were associated with airway measures or emphysema measures, respectively. In the a priori-specified candidate gene set, 13 of 196 candidate genes harbored a nearby single-nucleotide polymorphism significantly associated with an emphysema phenotype. Visual CT examination associations were robust to adjustment for semiautomated correlates in many cases.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.

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