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. 2024 Oct 10;64(6):2400968.
doi: 10.1183/13993003.00968-2024. Print 2024 Dec.

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

Chenghao Weng  1   2 , Yuxuan Zhao  3   2 , Mingyu Song  3 , Zilun Shao  3 , Yuanjie Pang  3 , Canqing Yu  3   4   5 , Pei Pei  4 , Ling Yang  6 , Iona Y Millwood  6 , Robin G Walters  6 , Yiping Chen  6 , Huaidong Du  6 , Junshi Chen  7 , Zhengming Chen  6 , Giulio Genovese  8   9   10 , Chikashi Terao  11   12   13 , Jun Lv  3   4   5 , Liming Li  3   4   5 , Dianjianyi Sun  14   4   5 ; China Kadoorie Biobank Collaborative Group
Affiliations

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

Chenghao Weng et al. Eur Respir J. .

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.

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Conflict of interest statement

Conflict of interest: The authors have no potential conflicts of interest to disclose.

Figures

None
Overview of the study design and findings. mLOY: mosaic loss of chromosome Y; IPF: idiopathic pulmonary fibrosis. #: expanded mLOY refers to mLOY carriers with affected cell fraction ≥10%.
FIGURE 1
FIGURE 1
Associations between mosaic loss of chromosome Y (mLOY) subtypes and lung diseases: a) all lung diseases; b) COPD, c) lung cancer and d) idiopathic pulmonary fibrosis (IPF). UKB: UK Biobank; CKB: China Kadoorie Biobank.
FIGURE 2
FIGURE 2
Joint association of mosaic loss of chromosome Y (mLOY) and smoking status with the risk of lung diseases in the UK Biobank: a) all lung diseases; b) COPD, c) lung cancer and d) idiopathic pulmonary fibrosis (IPF).
FIGURE 3
FIGURE 3
Joint association of mosaic loss of chromosome Y (mLOY) subtypes and smoking status with the risk of lung diseases the UK Biobank: a) all lung diseases, b) COPD, c) lung cancer and d) idiopathic pulmonary fibrosis (IPF).
See this image and copyright information in PMC

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