DSP variants may be associated with longitudinal change in quantitative emphysema

Woori Kim,Phuwanat Sakornsakolpat,David A Lynch,Edwin K Silverman,Terri H Beaty,Harvey O Coxson,Michael H Cho,Ruth Tal-Singer

doi:10.1186/s12931-019-1097-8

Abstract

BackgroundEmphysema, characterized by lung destruction, is a key component of Chronic Obstructive Pulmonary Disease (COPD) and is associated with increased morbidity and mortality. Genome-wide association studies (GWAS) have identified multiple genetic factors associated with cross-sectional measures of quantitative emphysema, but the genetic determinants of longitudinal change in quantitative measures of emphysema remain largely unknown. Our study aims to identify genetic variants associated with longitudinal change in quantitative emphysema measured by computed tomography (CT) imaging.MethodsWe included current and ex-smokers from two longitudinal cohorts: COPDGene, a study of Non-Hispanic Whites (NHW) and African Americans (AA), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE). We calculated annual change in two quantitative measures of emphysema based on chest CT imaging: percent low attenuation area (≤ − 950HU) (%LAA-950) and adjusted lung density (ALD). We conducted GWAS, separately in 3030 NHW and 1158 AA from COPDGene and 1397 Whites from ECLIPSE. We further explored effects of 360 previously reported variants and a lung function based polygenic risk score on annual change in quantitative emphysema.ResultsIn the genome-wide association analysis, no variants achieved genome-wide significance (P < 5e-08). However, in the candidate region analysis, rs2076295 in the DSP gene, previously associated with COPD, lung function and idiopathic pulmonary fibrosis, was associated with change in %LAA-950 (β (SE) = 0.09 (0.02), P = 3.79e-05) and in ALD (β (SE) = − 0.06 (0.02), P = 2.88e-03). A lung function based polygenic risk score was associated with annual change in %LAA-950 (P = 4.03e-02) and with baseline measures of quantitative emphysema (P < 1e-03) and showed a trend toward association with annual change in ALD (P = 7.31e-02).ConclusionsDSP variants may be associated with longitudinal change in quantitative emphysema. Additional investigation of the DSP gene are likely to provide further insights into the disease progression in emphysema and COPD.Trial registrationClinicaltrials.gov Identifier: NCT00608764, NCT00292552.

Highlights

Emphysema, characterized by lung destruction, is a key component of Chronic Obstructive Pulmonary Disease (COPD) and is associated with increased morbidity and mortality
Longitudinal change in quantitative emphysema is associated with spirometric measures of lung function, severity of COPD and ongoing smoking, and as such has been proposed as a marker of response to therapy for COPD [6]
Our study aims to examine genetic variants for association with change in quantitative emphysema measured by computed tomography (CT) imaging from two longitudinal cohort studies: COPDGene and Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE)

Summary

Introduction

Emphysema, characterized by lung destruction, is a key component of Chronic Obstructive Pulmonary Disease (COPD) and is associated with increased morbidity and mortality. Our study aims to identify genetic variants associated with longitudinal change in quantitative emphysema measured by computed tomography (CT) imaging. Emphysema, characterized by the destruction of lung parenchyma, is a key component of COPD and associated with increased morbidity and mortality. Advances in computed tomography (CT) imaging provide the opportunity to assess the extent and progression of emphysema quantitatively, and to study its related risk factors. Longitudinal change in quantitative emphysema is associated with spirometric measures of lung function, severity of COPD and ongoing smoking, and as such has been proposed as a marker of response to therapy for COPD [6]

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