DSP variants may be associated with longitudinal change in quantitative emphysema

被引：10

作者：

Kim, Woori ^{[1
,2
]}

Cho, Michael H. ^{[2
,3
]}

Sakornsakolpat, Phuwanat ^{[2
,4
]}

Lynch, David A. ^{[5
]}

Coxson, Harvey O. ^{[6
]}

Tal-Singer, Ruth ^{[7
]}

Silverman, Edwin K. ^{[2
,3
]}

Beaty, Terri H. ^{[1
]}

机构：

[1] Johns Hopkins Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA

[2] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[3] Brigham & Womens Hosp, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA

[4] Mahidol Univ, Fac Med, Siriraj Hosp, Dept Med, Bangkok, Thailand

[5] Natl Jewish Hlth, Dept Radiol, Denver, CO USA

[6] Univ British Columbia, Dept Radiol, Columbia, BC, Canada

[7] GSK, Collegeville, PA USA

来源：

RESPIRATORY RESEARCH | 2019年 / 20卷 / 1期

关键词：

GWAS; Genetics; Emphysema; Emphysema progression; COPD; GENOME-WIDE ASSOCIATION; OBSTRUCTIVE PULMONARY-DISEASE; COMPUTED-TOMOGRAPHY; LUNG-FUNCTION; DESMOPLAKIN; DENSITY; COPD; LOCI; HERITABILITY; DENSITOMETRY;

D O I：

10.1186/s12931-019-1097-8

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

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 (beta (SE) = 0.09 (0.02), P = 3.79e-05) and in ALD (beta (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.

引用

页数：10

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