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Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema.

Abstract：

RATIONALE:chronic obstructive pulmonary disease (COPD), characterized by airflow limitation, is a disorder with high phenotypic and genetic heterogeneity. Pulmonary emphysema is a major but variable component of COPD; familial data suggest that different components of COPD, such as emphysema, may be influenced by specific genetic factors. OBJECTIVES:to identify genetic determinants of emphysema assessed through high-resolution chest computed tomography in individuals with COPD. METHODS:we performed a genome-wide association study (GWAS) of emphysema determined from chest computed tomography scans with a total of 2,380 individuals with COPD in three independent cohorts of white individuals from (1) a cohort from Bergen, Norway, (2) the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study, and (3) the National Emphysema Treatment Trial (NETT). We tested single-nucleotide polymorphism associations with the presence or absence of emphysema determined by radiologist assessment in two of the three cohorts and a quantitative emphysema trait (percentage of lung voxels less than -950 Hounsfield units) in all three cohorts. MEASUREMENTS AND MAIN RESULTS:we identified association of a single-nucleotide polymorphism in BICD1 with the presence or absence of emphysema (P = 5.2 × 10(-7) with at least mild emphysema vs. control subjects; P = 4.8 × 10(-8) with moderate and more severe emphysema vs. control subjects). CONCLUSIONS:our study suggests that genetic variants in BICD1 are associated with qualitative emphysema in COPD. Variants in BICD1 are associated with length of telomeres, which suggests that a mechanism linked to accelerated aging may be involved in the pathogenesis of emphysema. Clinical trial registered with www.clinicaltrials.gov (NCT00292552).

journal_name

Am J Respir Crit Care Med

journal_title

American journal of respiratory and critical care medicine

authors

Kong X,Cho MH,Anderson W,Coxson HO,Muller N,Washko G,Hoffman EA,Bakke P,Gulsvik A,Lomas DA,Silverman EK,Pillai SG,ECLIPSE Study NETT Investigators.

doi

10.1164/rccm.201004-0541OC

subject

Has Abstract

pub_date

2011-01-01 00:00:00

pages

43-9

issue

eissn

1073-449X

issn

1535-4970

pii

201004-0541OC

journal_volume

183

pub_type

临床试验,杂志文章

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Genome-wide association study identifies BICD1 as a susceptibility gene for emphysema.