Department of Biostatistics and Epidemiology, School of Health, and Student Research Committee, Isfahan University of Medical Sciences, Isfahan, Iran.
Nutrition and Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti, Tehran, Iran; Department of Nutrition, School of Public Health, Iran University of Medical Sciences, Tehran, Iran.
Nutr Metab Cardiovasc Dis. 2024 May;34(5):1305-1313. doi: 10.1016/j.numecd.2024.02.013. Epub 2024 Feb 28.
The putative association between serum 25-hydroxyvitamin D concentration [25(OH)D] and the risk of cardioembolic stroke (CES) has been examined in observational studies, which indicate controversial findings. We performed Mendelian randomization (MR) analysis to determine the causal relationship of serum 25(OH)D with the risk of CES.
The summary statistics dataset on the genetic variants related to 25(OH)D was used from the published GWAS of European descent participants in the UK Biobank, including 417,580 subjects, yielding 143 independent loci in 112 1-Mb regions. GWAS summary data of CES was obtained from GIGASTROKE Consortium, which included European individuals (10,804 cases, 1,234,808 controls). Our results unveiled a causal relationship between 25(OH)D and CES using IVW [OR = 0.82, 95% CI: 0.67-0.98, p = 0.037]. Horizontal pleiotropy was not seen [MR-Egger intercept = 0.001; p = 0.792], suggesting an absence of horizontal pleiotropy. Cochrane's Q [Q = 78.71, p-value = 0.924], Rucker's Q [Q = 78.64, p-value = 0.913], and I = 0.0% (95% CI: 0.0%, 24.6%) statistic suggested no heterogeneity. This result remained consistent using different MR methods and sensitivity analyses, including Maximum likelihood [OR = 0.82, 95%CI: 0.67-0.98, p-value = 0.036], Constrained maximum likelihood [OR = 0.76, 95%CI: 0.64-0.90, p-value = 0.002], Debiased inverse-variance weighted [OR = 0.82, 95%CI: 0.68-0.99, p-value = 0.002], MR-PRESSO [OR = 0.82, 95%CI 0.77-0.87, p-value = 0.022], RAPS [OR = 0.82, 95%CI 0.67-0.98, p-value = 0.038], MR-Lasso [OR = 0.82, 95%CI 0.68-0.99, p-value = 0.037].
Our MR analysis provides suggestive evidence that increased 25(OH)D levels may play a protective role in the development of cardioembolic stroke. Determining the role of 25(OH)D in stroke subtypes has important clinical and public health implications.
血清 25-羟维生素 D 浓度[25(OH)D]与心源性栓塞性卒中（CES）风险之间的假定关联已在观察性研究中进行了研究，这些研究结果存在争议。我们进行了孟德尔随机化（MR）分析，以确定血清 25(OH)D 与 CES 风险之间的因果关系。
使用来自英国生物库中欧洲血统参与者的已发表 GWAS 的与 25(OH)D 相关的遗传变异汇总统计数据集，包括 417580 名受试者，在 112 个 1-Mb 区域中产生了 143 个独立的基因座。CES 的 GWAS 汇总数据来自 GIGASTROKE 联盟，其中包括欧洲个体（10804 例病例，1234808 例对照）。我们的结果使用 IVW 揭示了 25(OH)D 与 CES 之间的因果关系[OR=0.82，95%CI：0.67-0.98，p=0.037]。未观察到水平遗传异质性[MR-Egger 截距=0.001；p=0.792]，表明不存在水平遗传异质性。Cochrane's Q [Q=78.71，p 值=0.924]、Rucker's Q [Q=78.64，p 值=0.913]和 I=0.0%（95%CI：0.0%，24.6%）统计表明没有异质性。使用不同的 MR 方法和敏感性分析，包括最大似然[OR=0.82，95%CI：0.67-0.98，p 值=0.036]、约束最大似然[OR=0.76，95%CI：0.64-0.90，p 值=0.002]、去偏逆方差加权[OR=0.82，95%CI：0.68-0.99，p 值=0.002]、MR-PRESSO [OR=0.82，95%CI 0.77-0.87，p 值=0.022]、RAPS [OR=0.82，95%CI 0.67-0.98，p 值=0.038]和 MR-Lasso [OR=0.82，95%CI 0.68-0.99，p 值=0.037]，该结果仍然一致。
我们的 MR 分析提供了有说服力的证据，表明较高的 25(OH)D 水平可能在 CES 的发展中起保护作用。确定 25(OH)D 在卒中亚型中的作用具有重要的临床和公共卫生意义。
