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Am J Respir Crit Care Med. 2011 Jan 1;183(1):43-9. doi: 10.1164/rccm.201004-0541OC. Epub 2010 Aug 13.

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

Author information

1
Research and Development, GlaxoSmithKline, 709 Swedeland Road, UW2230, King of Prussia, PA 19406, USA. xiangyang.q.kong@gsk.com

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).

PMID:
20709820
PMCID:
PMC3040393
DOI:
10.1164/rccm.201004-0541OC
[Indexed for MEDLINE]
Free PMC Article

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