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Open Access 01-12-2019 | Computed Tomography | Research

DSP variants may be associated with longitudinal change in quantitative emphysema

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

Published in: Respiratory Research | Issue 1/2019

Abstract

Background

Emphysema, 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.

Methods

We 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.

Results

In 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).

Conclusions

DSP 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 registration

Clinicaltrials.gov Identifier: NCT00608764, NCT00292552.

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Title: DSP variants may be associated with longitudinal change in quantitative emphysema
Authors: Woori Kim
Michael H. Cho
Phuwanat Sakornsakolpat
David A. Lynch
Harvey O. Coxson
Ruth Tal-Singer
Edwin K. Silverman
Terri H. Beaty
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Computed Tomography
Computed Tomography
Chronic Obstructive Lung Disease
Published in: Respiratory Research / Issue 1/2019
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-019-1097-8

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