Interaction between Smoking and genetic risk of FEV1/FVC ratio in chronic lung disease: a cross-sectional study

J Korean Soc Res Nicotine Tob

Published online March 17, 2023

Su Hyun Lee ^{1, 2}, Ji Woo Beak ^{1, 2}, Sun Ha Jee ^{1, 2, *

¹Department of Epidemiology and Health Promotion, Institute for Health Promotion, Graduate School of Public Health, Yonsei University, Seoul, Korea
²Department of Public Health, Graduate School, Yonsei University, Seoul, Korea}

Correspondence to: Sun Ha Jee, 서울특별시 서대문구 연세로 50-1, 우편번호: 03722, 전화: 02-2228-1523, 이메일: jsunha@yuhs.ac

Abstract: Background
Although both lung function and smoking are risk factors for Chronic Lung Disease (CLD), it is unclear whether the Genetic Risk Score (GRS) of lung function is linked to CLD prevalence and whether smoking has a synergistic effect. We wanted to see if there was an association between GRS for FEV1/FVC and CLD, and if so, how smoking affected that association.
Methods
After performing a Genome-Wide Association Study (GWAS) of the FEV1/FVC, we generated FEV1/FVC-related GRS. Multivariable regression was used to estimate the Odds Ratio (OR) and 95% confidence intervals for the association of GRS for FEV1/FVC with smoking and CLD.
Results
This study included 8,166 participants (mean of age 52.18 years, 53.45% female). GRS, which contained 62 significant single nucleotide polymorphisms (SNPs) for the FEV1/FVC across the genome, showed a strong association with CLD. The OR of those in the genetically low lung function and the heavy smoking group was 3.01 times (95% CI 1.07-10.7) than in the genetically high lung function and heavy smoking group. Although there was no significant interaction between GRS for CLD prevalence and smoking status (p for interaction 0.44), the OR for former smokers with genetically low lung function compared to non-smokers with genetically high lung function was 4.29 (95%). CI 1.20 -17.1).
Conclusions
The lung function of GRS, which was composed of significant SNPs in the GWAS for FEV1/FVC, demonstrated a significant association 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