Genome-Wide Association Analysis of Rapid Decline in Lung Function: Analysis From the Korean Genome and Epidemiology Study

Abstract

Background: A rapid decline in forced expiratory volume in 1 second (FEV1) is considered an important phenotype of the development of chronic obstructive pulmonary disease (COPD). However, the associations between specific genetic variants (single-nucleotide polymorphisms; SNPs) and this phenotype remain uncertain. Methods: We enrolled 6,516 individuals from the Korean Genome and Epidemiology Study (KoGES). A rapid decline in FEV1 was defined as an annual decrease of FEV1 >= 60 mL/year. A multivariable logistic regression model was used to assess the associations between SNP variants and the rapid decline in FEV1. Considering the significant impact of smoking on lung function, a subgroup analysis based on smoking history was also conducted. Results: A genome-wide association analysis of the rapid decline in FEV1 identified 15 association signals (P < 5.0 x 10(-8)). Among the 15 nucleotide variants, rs9833533 and rs1496255 have been previously reported to be associated with lung function development. In the subgroup analysis, rs16951883 (adjusted odds ratio [aOR], 3.24; P = 5.87 x 10-8) was the most significant SNP associated with rapid decline in FEV1 among never smokers, followed by rs41476549, rs16840064, and rs1350110. Conversely, among ever smokers, rs10959478 (aOR, 4.74; P = 8.27 x 10(-7)) showed the highest significance, followed by rs6805861, rs9833533, and rs16906215. Conclusion: We identified 15 nucleotide variants linked to a rapid decline in FEV1, including two SNPs previously reported to be associated with lung function development. Additional SNPs, which were associated with COPD, may be found using novel phenotypes.