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


OBJECTIVE
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.


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).
Kong
Xiangyang
X
Research and Development, GlaxoSmithKline, 709 Swedeland Road, UW2230, King of Prussia, PA 19406, USA. xiangyang.q.kong@gsk.com
Cho
Michael H
MH
Anderson
Wayne
W
Coxson
Harvey O
HO
Muller
Nestor
N
Washko
George
G
Hoffman
Eric A
EA
Bakke
Per
P
Gulsvik
Amund
A
Lomas
David A
DA
Silverman
Edwin K
EK
Pillai
Sreekumar G
SG
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods*; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications / Q000175:diagnosis; D011656:Pulmonary Emphysema / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D013147:Spirometry; D014057:Tomography, X-Ray Computed
D048868:Adaptor Proteins, Signal Transducing; C109571:BICD1 protein, human; D003598:Cytoskeletal Proteins; D004247:DNA