Pan Weicong, Huang Zhanqiang, Deng Haiyan, Huang He, Yu Ke
Department of Emergency Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen Second People's Hospital, Shenzhen, China.
Department of General Medicine, Affiliated Hospital of Chengde Medical College, Chengde, China.
Medicine (Baltimore). 2024 Dec 6;103(49):e40824. doi: 10.1097/MD.0000000000040824.
Observational studies have reported an association between Vitamin D deficiency and an increased risk of bronchiectasis. This study aims to investigate the causal relationship between Vitamin D levels and bronchiectasis using a 2-sample Mendelian randomization (MR) analysis. Data from 2 genome-wide association studies (GWAS) based on European ancestry were analyzed: serum vitamin D levels (sample size = 441,291 [UK Biobank]) and bronchiectasis (sample size = 187,830 [cases = 1107, controls = 186,723; FinnGen]). Inverse-variance weighted (IVW) analysis was primarily used to assess the causal effect of 25(OH)D levels on bronchiectasis, supplemented by Mendelian randomization Egger regression (MR-Egger), weighted median, simple mode, and weighted mode analyses. Additionally, MR-Egger intercept test and MR-Pleiotropy Residual Sum and Outlier methods were implemented to determine pleiotropy, and Cochran's Q test was conducted for heterogeneity testing. Leave-one-out analysis and Bayesian weighted Mendelian randomization was also used to assess the robustness of the results. The MR analysis suggested no significant causal effects of serum 25(OH)D levels on bronchiectasis using the IVW method (odds ratio = 1.550; 95% confidence interval [CI]: 0.908-2.315; P = .120). These results were consistent across MR-Egger regression, weighted median, simple mode, and weighted mode analyses. No significant heterogeneity, pleiotropy, or bias was detected in instrumental variables. Additionally, no evidence supported the causal effects of bronchiectasis on serum vitamin D levels (β = -0.002, 95% CI: -0.007 to 0.003; P = .463). Our study found no significant causal association between serum 25(OH)D levels and bronchiectasis, in either direction. A larger sample-sized randomized controlled trial (RCT) is needed to further investigate this potential causal relationship.
观察性研究报告称维生素D缺乏与支气管扩张风险增加之间存在关联。本研究旨在通过两样本孟德尔随机化（MR）分析来探究维生素D水平与支气管扩张之间的因果关系。分析了两项基于欧洲血统的全基因组关联研究（GWAS）的数据：血清维生素D水平（样本量=441,291[英国生物银行]）和支气管扩张（样本量=187,830[病例=1107，对照=186,723；芬兰基因库]）。主要采用逆方差加权（IVW）分析来评估25（OH）D水平对支气管扩张的因果效应，并辅以孟德尔随机化Egger回归（MR-Egger）、加权中位数、简单模式和加权模式分析。此外，实施MR-Egger截距检验和MR-多效性残差和离群值方法来确定多效性，并进行Cochran's Q检验以进行异质性检验。还采用留一法分析和贝叶斯加权孟德尔随机化来评估结果的稳健性。MR分析表明，使用IVW方法时，血清25（OH）D水平对支气管扩张无显著因果效应（优势比=1.550；95%置信区间[CI]：0.908-2.315；P=0.120）。这些结果在MR-Egger回归、加权中位数、简单模式和加权模式分析中是一致的。在工具变量中未检测到显著的异质性、多效性或偏倚。此外，没有证据支持支气管扩张对血清维生素D水平的因果效应（β=-0.002，95%CI：-0.007至0.003；P=0.463）。我们的研究发现血清25（OH）D水平与支气管扩张之间在两个方向上均无显著因果关联。需要进行更大样本量的随机对照试验（RCT）来进一步研究这种潜在的因果关系。
