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Ann Am Thorac Soc. 2017 Jan;14(1):33-40. doi: 10.1513/AnnalsATS.201606-427OC.

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

Author information

1
1 Computational Biosciences Program, University of Colorado, Denver, Aurora, Colorado.
2
2 National Jewish Health, Denver, Colorado; and.
3
3 Channing Division of Network Medicine.
4
4 Division of Pulmonary and Critical Care Medicine.
5
5 Surgical Planning Laboratory, and.
6
6 Division of General Internal Medicine and Primary Care, Brigham and Women's Hospital, Boston, Massachusetts.

Abstract

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 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.

KEYWORDS:

airway remodeling; emphysema; genomics; radiology

PMID:
27739898
PMCID:
PMC5291477
DOI:
10.1513/AnnalsATS.201606-427OC
[Indexed for MEDLINE]
Free PMC Article

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