Genome-wide association study of lung function and clinical implication in heavy smokers

  • Xingnan Li (Contributor)
  • Victor E. Ortega (Creator)
  • Elizabeth J. Ampleford (Creator)
  • R. Graham Barr (Contributor)
  • Stephanie A. Christenson (Creator)
  • Christopher B. Cooper (Creator)
  • David Couper (Creator)
  • M. T. Dransfield (Creator)
  • Nadia N. Hansel (Creator)
  • Eric A. Hoffman (Creator)
  • Richard E. Kanner (Creator)
  • Eric C. Kleerup (Creator)
  • Fernando J. Martinez (Creator)
  • Robert Paine (Creator)
  • Prescott G. Woodruff (Contributor)
  • Greg A. Hawkins (Creator)
  • Eugene Bleecker (Creator)
  • Deborah Meyers (Creator)
  • Victor Ortega (Creator)
  • David Couper (Creator)
  • Mark B. Dransfield (Creator)
  • Nadia Hansel (Creator)
  • E. Hoffman (Creator)
  • R. E. Kanner (Creator)
  • Eric Kleerup (Creator)
  • Fernando Martinez (Creator)
  • Robert Paine (Creator)
  • Eugene R. Bleecker (Creator)
  • Deborah Meyers (Creator)



Abstract Background The aim of this study is to identify genetic loci associated with post-bronchodilator FEV1/FVC and FEV1, and develop a multi-gene predictive model for lung function in COPD. Methods Genome-wide association study (GWAS) of post-bronchodilator FEV1/FVC and FEV1 was performed in 1645 non-Hispanic White European descent smokers. Results A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV1/FVC (p = 1.2 × 10− 8) and FEV1 (p = 2.1 × 10− 9). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10− 4) and severity (OR = 4.1; p = 0.0036). Heterozygous subjects (CT genotype) had significantly lower lung function and higher percentage of COPD and more severe COPD than subjects with the CC genotype. 8.6% of the variance of post-bronchodilator FEV1/FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P 
Date made available2018

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