白细胞端粒长度与肺功能：一项欧洲人群的孟德尔随机化研究
Leukocyte telomere length and lung function: a mendelian randomization study in European population.
作者信息
Zhu Shenyu, Zheng Wenlong, Rao Dingyu, Tang Zhixian, Liao Xinhui
机构信息
Department of Thoracic Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
Cardiothoracic Surgery Brain injury and brain protection key laboratory of Ganzhou, Jiangxi, China.
出版信息
Front Physiol. 2024 Oct 24;15:1373064. doi: 10.3389/fphys.2024.1373064. eCollection 2024.
BACKGROUND
The telomere has long been regarded as a dependable biomarker for cellular senescence. The lung function can reflect the function and status of the lungs. As individuals age beyond adulthood, there is a gradual decline in lung function. However, the existence of a associated between leukocyte telomere length (LTL) and lung function remains uncertain.
METHODS
A two-sample Mendelian randomization (MR) analysis was used. The Single-nucleotide polymorphisms (SNPs) of LTL from the genome-wide association (GWAS) study were used as exposure instruments variable, and the lung function indicator including Forced expiratory volume in 1-s (FEV1), FEV1 Best measure, FEV1 predicted and Forced vital capacity (FVC) from the Neale Lab and MRC-IEU were used as outcomes. The associated between the exposures and outcomes was assessed using inverse-variance weighted (IVW), MR-Egger, and weighted median methods. Sensitivity analysis was conducted using Cochran's Q-test, MR-Egger intercept test, MR-PRESSO, leave-one-out analysis, and Steriger test.
RESULTS
Using the IVW method, a significant association was identified between genetically determined telomere length extension and enhanced lung function in FEV1, with ukb-a-336 (P = 0.127, OR = 1.028,95CI% = 1.003-1.042) and ukb-b-19657 (P = 7.26E-05, OR = 1.051,95CI% = 1.025-1.077),in FEV1 predicted, ukb-a-234 (P = 0.013, OR = 1.029,95CI% = 1.003-1.042), ukb-b-8428 (P = 0.001, OR = 1.032,95CI% = 1.012-1.052), in FEV1 best measure, ukb-a-231 (P = 7.24E-05, OR = 1.050,95CI% = 1.025-1.075), ukb-b-11141 (P = 1.40E-09, OR = 1.067,95CI% = 1.045-1.090).The sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy.Meanwhile, the Steriger test results also indicate that the directionality between exposure and outcome is correct. Therefore, the results indicated robustness.
CONCLUSION
There is a correlation between longer LTL and better lung function in the European dataset.
背景
长期以来，端粒一直被视为细胞衰老的可靠生物标志物。肺功能可以反映肺的功能和状态。随着个体成年后年龄增长，肺功能会逐渐下降。然而，白细胞端粒长度（LTL）与肺功能之间是否存在关联仍不确定。
方法
采用两样本孟德尔随机化（MR）分析。全基因组关联（GWAS）研究中LTL的单核苷酸多态性（SNP）用作暴露工具变量，来自Neale实验室和MRC - IEU的肺功能指标包括第1秒用力呼气量（FEV1）、最佳FEV1测量值、预测FEV1和用力肺活量（FVC）用作结局。使用逆方差加权（IVW）、MR-Egger和加权中位数方法评估暴露与结局之间的关联。使用 Cochr an's Q检验、MR-Egger截距检验、MR-PRESSO、留一法分析和Steriger检验进行敏感性分析。
结果
使用IVW方法，在基因决定的端粒长度延长与FEV1肺功能增强之间发现显著关联，ukb-a-336（P = 0.127，OR = 1.028，95%CI = 1.003 - 1.042）和ukb-b-19657（P = 7.26E-05，OR = 1.051，95%CI = 1.025 - 1.077）；在预测FEV1方面，ukb-a-234（P = 0.013，OR = 1.029，95%CI = 1.003 - 1.042），ukb-b-8428（P = 0.001，OR = 1.032，95%CI = 1.012 - 1.052）；在最佳FEV1测量值方面，ukb-a-231（P = 7.24E-05，OR = 1.050，95%CI = 1.025 - 1.075），ukb-b-11141（P = 1.40E-09，OR = 1.067，95%CI = 1.045 - 1.090）。敏感性分析未发现异质性或水平多效性。同时，Steriger检验结果也表明暴露与结局之间的方向性是正确的。因此，结果显示出稳健性。
结论
在欧洲数据集中，较长的LTL与较好的肺功能之间存在相关性。
Zotero 插件