Mosaic Loss of Chromosome Y, Tobacco Smoking and Risk of Age-related Lung Diseases: Insights from Two Prospective Cohorts

Overview

Journal Eur Respir J

Specialty Pulmonary Medicine

Date 2024 Oct 14

PMID 39401857

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

Affiliations

Soon will be listed here.

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.

Citing Articles

A complex systems approach to mosaic loss of the Y chromosome.

Guo X, Dai X Geroscience. 2024; 47(1):631-651.

PMID: 39680277 PMC: 11872822. DOI: 10.1007/s11357-024-01468-7.

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