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

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


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 (NCT00292552).

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • DNA / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study / methods*
  • Genotype
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Emphysema / diagnosis
  • Pulmonary Emphysema / etiology
  • Pulmonary Emphysema / genetics*
  • Spirometry
  • Tomography, X-Ray Computed


  • Adaptor Proteins, Signal Transducing
  • BICD1 protein, human
  • Cytoskeletal Proteins
  • DNA

Associated data