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

The aim of this study is to identify genetic loci associated with post-bronchodilator FEV /FVC and FEV , and develop a multi-gene predictive model for lung function in COPD. Genome-wide association study (GWAS) of post-bronchodilator FEV /FVC and FEV was performed in 1645 non-Hispanic White European descent smokers. A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV /FVC (p = 1.2 × 10 ) and FEV (p = 2.1 × 10 ). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10 ) 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 FEV /FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P