Journal article
Genome-wide Association Study Identifies BICD1 as a Susceptibility Gene for Emphysema
American journal of respiratory and critical care medicine, Vol.183(1), pp.43-49
01/01/2011
DOI: 10.1164/rccm.201004-0541OC
PMCID: PMC3040393
PMID: 20709820
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).
Details
- Title: Subtitle
- Genome-wide Association Study Identifies BICD1 as a Susceptibility Gene for Emphysema
- Creators
- Xiangyang Kong - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaMichael H Cho - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaWayne Anderson - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaHarvey O Coxson - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaNestor Muller - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaGeorge Washko - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaEric A Hoffman - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaPer Bakke - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaAmund Gulsvik - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaDavid A Lomas - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaEdwin K Silverman - GlaxoSmithKline Research and Development, King of Prussia, PennsylvaniaSreekumar G Pillai - GlaxoSmithKline Research and Development, King of Prussia, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- American journal of respiratory and critical care medicine, Vol.183(1), pp.43-49
- DOI
- 10.1164/rccm.201004-0541OC
- PMID
- 20709820
- PMCID
- PMC3040393
- NLM abbreviation
- Am J Respir Crit Care Med
- ISSN
- 1073-449X
- eISSN
- 1535-4970
- Publisher
- American Thoracic Society
- Language
- English
- Date published
- 01/01/2011
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Internal Medicine
- Record Identifier
- 9984051988602771
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