Weng Chenghao, Zhao Yuxuan, Song Mingyu, Shao Zilun, Pang Yuanjie, Yu Canqing, Pei Pei, Yang Ling, Millwood Iona Y, Walters Robin G, Chen Yiping, Du Huaidong, Chen Junshi, Chen Zhengming, Genovese Giulio, Terao Chikashi, Lv Jun, Li Liming, Sun Dianjianyi
School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China.
These authors contributed equally to this work.
Eur Respir J. 2024 Oct 10;64(6). doi: 10.1183/13993003.00968-2024. Print 2024 Dec.
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.
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 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.
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.
Y染色体镶嵌性缺失（mLOY）是老年男性中最常见的染色体改变，关于其与年龄相关性肺部疾病风险之间的潜在关系，人们了解甚少。
我们纳入了来自英国生物银行（UKB）的217780名参与者以及来自中国嘉道理生物银行的42859名参与者。使用镶嵌染色体改变（MoChA）流程检测mLOY事件。结局包括所有肺部疾病、慢性阻塞性肺疾病（COPD）、肺癌和特发性肺纤维化（IPF）。采用Cox比例风险模型来估计两个队列中mLOY与肺部疾病相关的风险比及95%置信区间。合并风险比通过荟萃分析得出。
两个队列的结果显示，扩大的mLOY与所有肺部疾病风险增加相关（风险比1.19（95%置信区间1.04 - 1.36））、COPD（风险比1.20（95%置信区间1.13 - 1.28））、肺癌（风险比1.34（95%置信区间1.21 - 1.48））以及在UKB队列中的IPF（风险比1.34（95%置信区间1.16 - 1.56））。有证据表明mLOY与吸烟行为之间存在正向交互作用（交互作用导致的相对超额风险（97.5%置信区间）>0）。此外，我们观察到在两个队列中，有扩大mLOY的当前吸烟者发生肺部疾病的风险最高。
mLOY可能是年龄相关性肺部疾病的一种新的预测指标。对于携带mLOY的当前吸烟者，采取戒烟行为可能有助于大幅降低其发生肺部疾病的风险。
