J Korean Med Sci.  2024 Nov;39(42):e275. 10.3346/jkms.2024.39.e275.

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

• Kim SH
• Lee H
• Jo YS
• Yoo J
• Choi JY

• KMID: 2560620
• DOI: http://doi.org/10.3346/jkms.2024.39.e275

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 × 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 × 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 × 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.

Keyword

Pulmonary Disease; Chronic Obstructive; Respiratory Function Tests; Spirometry; Genetic Techniques; Genome-Wide Association Study; KoGES

Figure

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  Fig. 1 Manhattan plots of the genome-wide association analysis of rapid decline in FEV1.The blue and red horizontal lines indicate possible significance (1 × 10−5) and the genome-wide threshold (5 × 10−8), respectively.FEV1 = forced expiratory volume in 1 second.

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