| Title: | Mosaic loss of chromosome Y, tobacco smoking and risk of age-related lung diseases: insights from two prospective cohorts |
| Journal: | European Respiratory Journal |
| Published: | 10 Oct 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/39401857/ |
| DOI: | https://doi.org/10.1183/13993003.00968-2024 |
Publication 13599
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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.</p>
METHODS: We included 217 780 participants from the UK Biobank and 42 859 participants from the China Kadoorie Biobank. The mLOY events were detected using the Mosaic Chromosomal Alterations pipeline. Outcomes included all lung diseases, chronic obstructive pulmonary disease (COPD), lung cancer, and idiopathic pulmonary fibrosis (IPF). Cox proportional hazard models were fitted to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of mLOY with lung diseases in both cohorts. The combined HRs were derived from meta-analysis.</p>
RESULTS: Results from two cohorts showed that expanded mLOY was associated with increased risks of all lung diseases [HR (95% CI): 1.19 (1.04, 1.37)], COPD [HR (95% CI): 1.20 (1.13, 1.28)], lung cancer [HR (95% CI): 1.34 (1.21, 1.48)], and IPF [HR (95% CI): 1.34 (1.16, 1.56) in UKB]. There was evidence of positive interactions between mLOY and smoking behavior [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.</p>
CONCLUSION: mLOY may be a novel predictor for age-related lung diseases. For current smokers carrying mLOY, adopting quitting smoking behavior may contribute to substantially reduce their risk of incident lung diseases.</p>
19 Authors
- Chenghao Weng
- Yuxuan Zhao
- Mingyu Song
- Zilun Shao
- Yuanjie Pang
- Canqing Yu
- Pei Pei
- Ling Yang
- Iona Y. Millwood
- Robin G. Walters
- Yiping Chen
- Huaidong Du
- Junshi Chen
- Zhengming Chen
- Giulio Genovese
- Chikashi Terao
- Jun Lv
- Liming Li
- Dianjianyi Sun
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