Department of Andrology, Guilin People's Hospital, Guilin, 541002, China.
Department of Urology, Guilin People's Hospital, Guilin, 541002, China.
Eur J Nutr. 2024 Nov 30;64(1):39. doi: 10.1007/s00394-024-03553-1.
In light of inconsistent evidence from previous observational studies regarding the correlation between serum vitamin D levels and urolithiasis, this study aimed to investigate the genome-wide causal association between genetically predicted serum 25(OH)D levels and urolithiasis using the Mendelian randomization (MR) approach.
In this study, we utilized genome-wide association studies (GWAS) summary statistics from the UK Biobank and SUNLIGHT consortium for serum vitamin D levels, as well as urolithiasis data from FinnGen. We employed bidirectional two-sample MR analysis to evaluate potential causal relationships. The primary MR analysis relied on the inverse variance weighted (IVW) method, supplemented by MR-Egger, weighted median, and weighted mode approaches. Sensitivity analyses were conducted to ensure result robustness, including Cochran's Q test, MR-Egger intercept test, leave-one-out tests, and MR pleiotropy residual sum and outlier (MR-PRESSO) test.
The MR analysis indicated no significant causal effects of serum 25(OH)D levels on urolithiasis [IVW method: (kidney and ureteral stones: OR = 1.134;95% CI, 0.953 to 1.350, p = 0.155; lower urinary tract stones: OR = 1.158; 95% CI, 0.806 to 1.666, p = 0.428)]. However, according to the IVW results, genetically predicted kidney and ureteral stones were associated with decreased serum 25(OH)D levels (beta = -0.025; 95% CI, -0.048 to -0.003; p = 0.028), while they did not indicate a causal effect of lower urinary tract stones on serum 25(OH)D levels (beta = -0.002; 95% CI, -0.013 to -0.008; p = 0.662). A sensitivity analysis suggested the robustness of these causal associations.
Our MR study did not provide evidence supporting a causal association between serum 25(OH)D levels and urolithiasis among individuals of European descent. However, there might exist a negative causal association between kidney and ureteral stones and serum 25(OH)D levels.
鉴于先前观察性研究中关于血清维生素 D 水平与尿石症之间相关性的证据不一致，本研究旨在使用孟德尔随机化（MR）方法，探究遗传预测的血清 25（OH）D 水平与尿石症之间的全基因组因果关联。
本研究利用英国生物库和 SUNLIGHT 联盟的全基因组关联研究（GWAS）汇总统计数据来获取血清维生素 D 水平的数据，以及 FinnGen 的尿石症数据。我们采用双向两样本 MR 分析来评估潜在的因果关系。主要的 MR 分析依赖于逆方差加权（IVW）方法，同时辅以 MR-Egger、加权中位数和加权模式方法。我们进行了敏感性分析，包括 Cochran's Q 检验、MR-Egger 截距检验、逐一排除检验和 MR 偏倚残差和异常值（MR-PRESSO）检验，以确保结果的稳健性。
MR 分析表明，血清 25（OH）D 水平与尿石症之间没有显著的因果关系（IVW 方法：（肾脏和输尿管结石：OR=1.134；95%CI，0.953 至 1.350，p=0.155；下尿路结石：OR=1.158；95%CI，0.806 至 1.666，p=0.428））。然而，根据 IVW 结果，遗传预测的肾脏和输尿管结石与血清 25（OH）D 水平降低相关（β=-0.025；95%CI，-0.048 至 -0.003；p=0.028），而不存在下尿路结石对血清 25（OH）D 水平的因果效应（β=-0.002；95%CI，-0.013 至 -0.008；p=0.662）。敏感性分析表明这些因果关联具有稳健性。
本 MR 研究未提供证据支持欧洲血统个体中血清 25（OH）D 水平与尿石症之间存在因果关系。然而，肾脏和输尿管结石与血清 25（OH）D 水平之间可能存在负向因果关系。
