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

doi:10.1183/13993003.00968-2024

. 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 Song³, Zilun Shao³, Yuanjie Pang³, Canqing Yu^{3

4

5}, Pei Pei⁴, Ling Yang⁶, Iona Y Millwood⁶, Robin G Walters⁶, Yiping Chen⁶, Huaidong Du⁶, Junshi Chen⁷, Zhengming Chen⁶, 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

¹ School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
² These authors contributed equally to this work.
³ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
⁴ Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.
⁵ Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.
⁶ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁷ China National Center for Food Safety Risk Assessment, Beijing, China.
⁸ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁹ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Genetics, Harvard Medical School, Boston, MA, USA.
¹¹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
¹² Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
¹³ Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
¹⁴ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China dsun1@bjmu.edu.cn.

PMID: 39401857
PMCID: PMC11684423
DOI: 10.1183/13993003.00968-2024

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. 2024.

. 2024 Oct 10;64(6):2400968.

doi: 10.1183/13993003.00968-2024. Print 2024 Dec.

Authors

Affiliations

¹ School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
² These authors contributed equally to this work.
³ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China.
⁴ Peking University Center for Public Health and Epidemic Preparedness and Response, Beijing, China.
⁵ Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, China.
⁶ Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), Nuffield Department of Population Health, University of Oxford, Oxford, UK.
⁷ China National Center for Food Safety Risk Assessment, Beijing, China.
⁸ Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
⁹ Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁰ Department of Genetics, Harvard Medical School, Boston, MA, USA.
¹¹ Laboratory for Statistical and Translational Genetics, RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan.
¹² Clinical Research Center, Shizuoka General Hospital, Shizuoka, Japan.
¹³ Department of Applied Genetics, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
¹⁴ Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China dsun1@bjmu.edu.cn.

PMID: 39401857
PMCID: PMC11684423
DOI: 10.1183/13993003.00968-2024

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**
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**
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**
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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References

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[1] Schneider JL, Rowe JH, Garcia-de-Alba C, et al. . The aging lung: physiology, disease, and immunity. Cell 2021; 184: 1990–2019. doi:10.1016/j.cell.2021.03.005 - DOI - PMC - PubMed

[2] Schneider JL, Rowe JH, Garcia-de-Alba C, et al. . The aging lung: physiology, disease, and immunity. Cell 2021; 184: 1990–2019. doi:10.1016/j.cell.2021.03.005 - DOI - PMC - PubMed

[3] Cho SJ, Stout-Delgado HW. Aging and lung disease. Annu Rev Physiol 2020; 82: 433–459. doi:10.1146/annurev-physiol-021119-034610 - DOI - PMC - PubMed

[4] Cho SJ, Stout-Delgado HW. Aging and lung disease. Annu Rev Physiol 2020; 82: 433–459. doi:10.1146/annurev-physiol-021119-034610 - DOI - PMC - PubMed

[5] Arimura-Omori M, Kiyohara C, Yanagihara T, et al. . Association between telomere-related polymorphisms and the risk of IPF and COPD as a precursor lesion of lung cancer: findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) registry. Asian Pac J Cancer Prev 2020; 21: 667–673. doi:10.31557/APJCP.2020.21.3.667 - DOI - PMC - PubMed

[6] Arimura-Omori M, Kiyohara C, Yanagihara T, et al. . Association between telomere-related polymorphisms and the risk of IPF and COPD as a precursor lesion of lung cancer: findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) registry. Asian Pac J Cancer Prev 2020; 21: 667–673. doi:10.31557/APJCP.2020.21.3.667 - DOI - PMC - PubMed

[7] GBD Chronic Respiratory Disease Collaborators . Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med 2020; 8: 585–596. doi:10.1016/S2213-2600(20)30105-3 - DOI - PMC - PubMed

[8] GBD Chronic Respiratory Disease Collaborators . Prevalence and attributable health burden of chronic respiratory diseases, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med 2020; 8: 585–596. doi:10.1016/S2213-2600(20)30105-3 - DOI - PMC - PubMed

[9] GBD 2019 Diseases and Injuries Collaborators . Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396: 1204–1222. doi:10.1016/S0140-6736(20)30925-9 - DOI - PMC - PubMed

[10] GBD 2019 Diseases and Injuries Collaborators . Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet 2020; 396: 1204–1222. doi:10.1016/S0140-6736(20)30925-9 - DOI - PMC - PubMed

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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

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Medical

Abstract

Conflict of interest statement

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References

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