Meng Qiang, Huang Lu, Tao Kai, Liu Yong, Jing Jiangpeng, Wang Wen, Qin Huaizhou, Feng Dayun, Cai Qing
Department of Neurosurgery and Institute for Functional Brain Disorders, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Front Cell Dev Biol. 2020 Nov 11;8:590903. doi: 10.3389/fcell.2020.590903. eCollection 2020.
There has been an increased interest for observational studies or randomized controlled trials exploring the impact of calcium intake on cardiovascular diseases (CVD) including coronary artery disease (CAD) and ischemic stroke (IS). However, a direct relationship between total calcium intake and CVD has not been well established and remains controversial. Mendelian randomization (MR) studies have been performed to evaluate the causal association between serum calcium levels and CAD risk and found that increased serum calcium levels could increase the risk of CAD. However, MR analysis found no significant association between genetically higher serum calcium levels and IS as well as its subtypes. Hence, three MR studies reported inconsistent effects of serum calcium levels on CAD and IS. Here, we performed an updated MR study to investigate the association of serum calcium levels with the risk of IS using large-scale genome-wide association study (GWAS) datasets. We selected 14 independent genetic variants as the potential instrumental variables from a large-scale serum calcium GWAS dataset and extracted summary statistics corresponding to the 14 serum calcium genetic variants from the MEGASTROKE Consortium IS GWAS dataset. Interestingly, we found a significant association between serum calcium levels and IS risk using the robust inverse-variance weighted (IVW) and penalized robust IVW methods, with β = 0.243 and = 0.002. Importantly, the MR results from the robust MR-Egger and penalized robust MR-Egger methods further supported the causal association between serum calcium levels and IS risk, with β = 0.256 and = 0.005. Meanwhile, the estimates from other MR methods are also consistent with the above findings.
对于探索钙摄入量对包括冠状动脉疾病（CAD）和缺血性中风（IS）在内的心血管疾病（CVD）影响的观察性研究或随机对照试验，人们的兴趣日益浓厚。然而，总钙摄入量与CVD之间的直接关系尚未完全确立，仍存在争议。已进行孟德尔随机化（MR）研究以评估血清钙水平与CAD风险之间的因果关联，发现血清钙水平升高会增加CAD风险。然而，MR分析发现，遗传上较高的血清钙水平与IS及其亚型之间没有显著关联。因此，三项MR研究报告了血清钙水平对CAD和IS的影响不一致。在此，我们进行了一项更新的MR研究，以使用大规模全基因组关联研究（GWAS）数据集调查血清钙水平与IS风险的关联。我们从大规模血清钙GWAS数据集中选择了14个独立的基因变异作为潜在的工具变量，并从MEGASTROKE联盟IS GWAS数据集中提取了与这14个血清钙基因变异相对应的汇总统计数据。有趣的是，我们使用稳健的逆方差加权（IVW）和惩罚稳健IVW方法发现血清钙水平与IS风险之间存在显著关联，β = 0.243，P = 0.002。重要的是，稳健的MR-Egger和惩罚稳健的MR-Egger方法的MR结果进一步支持了血清钙水平与IS风险之间的因果关联，β = 0.256，P = 0.005。同时，其他MR方法的估计结果也与上述发现一致。
