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Interaction between Smoking and Genetic Risk of FEV1/FVC Ratio in Chronic Lung Disease: A Cross-Sectional Study
J Korean Soc Res Nicotine Tob 2023; 14(1): 1-8
Published online March 30, 2023
© 2023 The Korean Society for Research on Nicotine and Tobacco.

Su Hyun Lee1,2, Ji Woo Baek1, Sun Ha Jee1,2*

1Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, 2Department of Public Health, Graduate School, Yonsei University, Seoul, Korea
Correspondence to: *吏꽑븯
뿰꽭븰援 蹂닿굔븰썝 뿭븰嫄닿컯利앹쭊븰怨, 援誘쇨굔媛뺤쬆吏꾩뿰援ъ냼
Received December 26, 2022; Revised March 15, 2023; Accepted March 17, 2023.
This is an Open-Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, dis-tribution, and reproduction in any medium, provided the original work is properly cited.
Background: Although lung function and smoking are risk factors for chronic lung disease (CLD), it is unclear whether the genetic risk score (GRS) for lung function is related to CLD prevalence and whether smoking has a synergistic effect. This study aimed to investigate whether the GRS for the forced expiratory volume in one second to the forced vital capacity (FEV1/FVC) ratio is associated with CLD, and if so, how smoking affects this association.
Methods: A genome-wide association study (GWAS) of the FEV1/FVC ratio was conducted, and the GRS for the FEV1/FVC ratio was generated. Multivariable regression was performed to estimate the odds ratio (OR) and 95% confidence intervals (CI) for the association between GRS for the FEV1/FVC ratio and smoking and CLD.
Results: A total of 8,166 participants (mean of age 52.18 years, 53.45% female) were included in this study. GRS, which contained 62 significant single-nucleotide polymorphisms identified in the GWAS for the FEV1/FVC ratio, had a strong association with CLD. The OR for CLD of those in the genetically low lung function and heavy smoking group was 3.01 times higher than that in the genetically high lung function and heavy smoking group (95% CI 1.07-10.7). Although no significant interaction was observed between GRS for CLD prevalence and smoking status (p for interaction=0.44), the OR of CLD for former smokers with genetically low lung function was 4.29 compared with non-smokers with genetically high lung function (95% CI 1.20-17.1).
Conclusion: GRS for the FEV1/FVC ratio was significantly associated with CLD. Participants with genetically low lung function were more likely to develop CLD when exposed to smoking.
Keywords : Chronic lung disease; Cross-sectional study; Smoking; Genetic risk score; Lung function; Interaction
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