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.

中文翻译：

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血清 25 羟基维生素 D 浓度对心源性卒中的因果影响：来自两样本孟德尔随机化的证据

血清 25-羟基维生素 D 浓度 [25(OH)D] 与心源性卒中 (CES) 风险之间的假定关联已在观察性研究中得到检验，这表明了有争议的发现。我们进行了孟德尔随机化 (MR) 分析，以确定血清 25(OH)D 与 CES 风险的因果关系。与 25(OH)D 相关的遗传变异的汇总统计数据集来自英国生物银行已发表的欧洲血统参与者的 GWAS，包括 417,580 名受试者，在 112 个 1-Mb 区域产生 143 个独立基因座。 CES 的 GWAS 摘要数据来自 GIGASTROKE 联盟，其中包括欧洲个体（10,804 例病例，1,234,808 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]。未观察到水平多效性 [MR-Egger 截距 = 0.001； p = 0.792]，表明不存在水平多效性。 Cochrane 的 Q [Q = 78.71，p 值 = 0.924]、Rucker 的 Q [Q = 78.64，p 值 = 0.913] 和 I = 0.0%（95% CI：0.0%、24.6%）统计数据表明没有异质性。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]，该结果保持一致。 ，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]、MR-Lasso [OR = 0.82，95%CI 0.68–0.99，p 值 = 0.037]。我们的 MR 分析提供了提示性证据，表明 25(OH)D 水平升高可能在心源性卒中的发展中发挥保护作用。确定 25(OH)D 在中风亚型中的作用具有重要的临床和公共卫生意义。