Mosaic loss of chromosome Y, tobacco smoking, and risk of age-related lung diseases: insights from two prospective cohorts

Weng, C; Zhao, Y; Song, M; Shao, Z; Pang, Y; Yu, C; Pei, P; Yang, L; Millwood, IY; Walters, RG; Chen, Y; Du, H; Chen, J; Chen, Z; Genovese, G; Terao, C; Lv, J; Li, L; Sun, D

Journal article

Mosaic loss of chromosome Y, tobacco smoking, and risk of age-related lung diseases: insights from two prospective cohorts

Abstract:: Background
Little is known about the underlying relationship between mosaic loss of chromosome Y (mLOY), the most common chromosomal alterations in older men, and the risk of age-related lung diseases.
Methods
We included 217 780 participants from the UK Biobank (UKB) and 42 859 participants from the China Kadoorie Biobank. The mLOY events were detected using the Mosaic Chromosomal Alterations (MoChA) pipeline. Outcomes included all lung diseases, COPD, lung cancer and idiopathic pulmonary fibrosis (IPF). Cox proportional hazard models were fitted to estimate the hazard ratios and 95% confidence intervals of mLOY with lung diseases in both cohorts. The combined hazard ratios were derived from meta-analysis.
Results
Results from the two cohorts showed that expanded mLOY was associated with increased risks of all lung diseases (HR 1.19 (95% CI 1.04–1.36)), COPD (HR 1.20 (95% CI 1.13–1.28)), lung cancer (HR 1.34 (95% CI 1.21–1.48)) and IPF (HR 1.34 (95% CI 1.16–1.56) in the UKB). There was evidence of positive interactions between mLOY and smoking behaviour (relative excess risk due to interaction (97.5% CI) >0). Additionally, we observed that current smokers with expanded mLOY had the highest risk of incident lung diseases in both cohorts.
Conclusions
mLOY may be a novel predictor for age-related lung diseases. For current smokers carrying mLOY, adopting quitting smoking behaviour may contribute to substantially reducing their risk of incident lung diseases.

Publication status:: Published

Peer review status:: Peer reviewed

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APA Style

Weng, C., Zhao, Y., Song, M., Shao, Z., Pang, Y., Yu, C., Pei, P., Yang, L., Millwood, I. Y., Walters, R. G., Chen, Y., Du, H., Chen, J., Chen, Z., Genovese, G., Terao, C., Lv, J., Li, L., & Sun, D. (2024). Mosaic loss of chromosome Y, tobacco smoking, and risk of age-related lung diseases: insights from two prospective cohorts. European Respiratory Journal, 64(6).

MLA Style

Weng, C., et al. “Mosaic Loss of Chromosome Y, Tobacco Smoking, and Risk of Age-Related Lung Diseases: Insights from Two Prospective Cohorts.” European Respiratory Journal, vol. 64, no. 6, European Respiratory Society, 2024.

Chicago Style

Weng, C, Y Zhao, M Song, Z Shao, Y Pang, C Yu, P Pei, et al. 2024. “Mosaic Loss of Chromosome Y, Tobacco Smoking, and Risk of Age-Related Lung Diseases: Insights from Two Prospective Cohorts.” European Respiratory Journal 64 (6).
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