Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Department of Neurosurgery, Tongde Hospital of Zhejiang Province, Hangzhou, China.
CNS Neurosci Ther. 2023 Oct;29(10):3062-3067. doi: 10.1111/cns.14248. Epub 2023 May 5.
To investigate the causal role of serum magnesium and calcium in epilepsy or any of its subtypes through Mendelian randomization (MR) approach.
Single nucleotide polymorphisms (SNPs) associated with serum magnesium and calcium were used as the instrumental variables. MR analyses were performed using the summary-level data for epilepsy extracted from International League Against Epilepsy Consortium (15,212 cases and 29,677 controls) to obtain the causal estimates. The analyses were replicated using FinnGen data (7224 epilepsy cases and 208,845 controls), and a meta-analysis was then conducted.
The result of combined analyses showed that higher serum magnesium concentrations was associated with a reduced risk of overall epilepsy (odds ratios [OR] = 0.28, 95% confidence interval [CI], 0.12-0.62, p = 0.002). In ILAE, higher serum magnesium was suggestively associated with reduced risks of focal epilepsy (OR = 0.25, 95% CI 0.10-0.62, p = 0.003). However, the results cannot be repeated in sensitivity analyses. As for serum calcium, the results did not reach statistical significance with overall epilepsy (OR = 0.60, 95% CI, 0.31-1.17, p = 0.134). However, genetically predicted serum calcium concentrations showed an inverse association with risk of generalized epilepsy (OR = 0.35, 95% CI, 0.17-0.74, p = 0.006).
The current MR analysis did not support a causal relationship between serum magnesium and epilepsy, but showed a causally negative association between genetically determined serum calcium and generalized epilepsy.
通过孟德尔随机化（MR）方法研究血清镁和钙在癫痫或其任何亚型中的因果作用。
使用与血清镁和钙相关的单核苷酸多态性（SNP）作为工具变量。使用从国际抗癫痫联盟（ILAE）联盟（15212 例病例和 29677 例对照）中提取的癫痫综合水平数据进行 MR 分析，以获得因果估计值。使用芬兰遗传（FinnGen）数据（7224 例癫痫病例和 208845 例对照）对分析进行重复，并进行了荟萃分析。
联合分析的结果表明，较高的血清镁浓度与总体癫痫风险降低相关（比值比 [OR] = 0.28，95%置信区间 [CI]，0.12-0.62，p = 0.002）。在 ILAE 中，较高的血清镁与局灶性癫痫风险降低相关（OR = 0.25，95%CI 0.10-0.62，p = 0.003）。然而，在敏感性分析中，结果无法重复。至于血清钙，总体癫痫的结果没有达到统计学意义（OR = 0.60，95%CI，0.31-1.17，p = 0.134）。然而，遗传预测的血清钙浓度与全面性癫痫风险呈负相关（OR = 0.35，95%CI，0.17-0.74，p = 0.006）。
目前的 MR 分析不支持血清镁与癫痫之间存在因果关系，但表明遗传决定的血清钙与全面性癫痫之间存在因果负相关。
