title: Visual Assessment of Chest Computed Tomographic Images Is Independently Useful for Genetic Association Analysis in Studies of Chronic Obstructive Pulmonary Disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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 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.
  
  
  CONCLUSIONS
  Standardized 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.
authors.affiliation: 1 Computational Biosciences Program, University of Colorado, Denver, Aurora, Colorado.|2 National Jewish Health, Denver, Colorado; and.
authors.forename: Eitan
authors.initials: E
authors.lastname: Halper-Stromberg
authors.affiliation: 3 Channing Division of Network Medicine.|4 Division of Pulmonary and Critical Care Medicine.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.affiliation: 2 National Jewish Health, Denver, Colorado; and.
authors.forename: Carla
authors.initials: C
authors.lastname: Wilson
authors.affiliation: 2 National Jewish Health, Denver, Colorado; and.
authors.forename: Dipti
authors.initials: D
authors.lastname: Nevrekar
authors.affiliation: 2 National Jewish Health, Denver, Colorado; and.
authors.forename: James D
authors.initials: JD
authors.lastname: Crapo
authors.affiliation: 4 Division of Pulmonary and Critical Care Medicine.
authors.forename: George
authors.initials: G
authors.lastname: Washko
authors.affiliation: 5 Surgical Planning Laboratory, and.
authors.forename: Raúl San José
authors.initials: RS
authors.lastname: Estépar
authors.affiliation: 2 National Jewish Health, Denver, Colorado; and.
authors.forename: David A
authors.initials: DA
authors.lastname: Lynch
authors.affiliation: 3 Channing Division of Network Medicine.|4 Division of Pulmonary and Critical Care Medicine.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: 2 National Jewish Health, Denver, Colorado; and.
authors.forename: Sonia
authors.initials: S
authors.lastname: Leach
authors.affiliation: 3 Channing Division of Network Medicine.|6 Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Castaldi
mesh_terms: D000368:Aged; D056151:Airway Remodeling; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D007091:Image Processing, Computer-Assisted; D016014:Linear Models; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000000981:diagnostic imaging* / Q000235:genetics; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000235:genetics; D014057:Tomography, X-Ray Computed; D044465:White People / Q000235:genetics
keywords: airway remodeling; emphysema; genomics; radiology