Abstract：
Vitamin D (Vit-D), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) are the major calciotropic hormones involved in the regulation of blood calcium levels from the intestine, kidney, and bone through a tight endocrine feedback loop system. Altered levels of calcium itself or through the effect of its regulatory hormones could affect blood pressure (BP), but the exact mechanisms remain unclear.
To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a two-sample Mendelian randomization (MR) study.
From 4 large genome-wide association studies (GWAS) we obtained independent (r2 < 0.001) single nucleotide polymorphisms (SNPs) associated with serum calcium (119 SNPs), Vit-D (78 SNPs), PTH (5 SNPs), and FGF23 (5 SNPs), to investigate through MR their association with systolic BP (SBP) and diastolic BP (DBP) in a Swedish urban-based study, the Malmö Diet and Cancer study (n = 29 298). Causality was evaluated by the inverse variance weighted method (IVW) and weighted median, while MR Egger and MR-PRESSO were used as sensitivity analyses.
Genetically predicted serum calcium level was found to be associated with DBP (IVW: beta = 0.10, SE = 0.04, P = 0.007) and SBP (IVW: beta = 0.07, SE = 0.04, P = 0.04). Genetically predicted Vit-D and PTH showed no association with the traits, while FGF23 was inversely associated with SBP (IVW: beta = -0.11, SE = 0.04, P = 0.01), although this association lost statistical significance in sensitivity analysis.
Our study shows a direct association between genetically predicted calcium level and DBP, and a weaker association with SBP. No such clear association was found for genetically predicted calciotropic hormone levels. It is of interest to detect which target genes involved in calcium homeostasis mediate the effect of calcium on BP, particularly for improving personalized intervention strategies.
To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a two-sample Mendelian randomization (MR) study.
From 4 large genome-wide association studies (GWAS) we obtained independent (r2 < 0.001) single nucleotide polymorphisms (SNPs) associated with serum calcium (119 SNPs), Vit-D (78 SNPs), PTH (5 SNPs), and FGF23 (5 SNPs), to investigate through MR their association with systolic BP (SBP) and diastolic BP (DBP) in a Swedish urban-based study, the Malmö Diet and Cancer study (n = 29 298). Causality was evaluated by the inverse variance weighted method (IVW) and weighted median, while MR Egger and MR-PRESSO were used as sensitivity analyses.
Genetically predicted serum calcium level was found to be associated with DBP (IVW: beta = 0.10, SE = 0.04, P = 0.007) and SBP (IVW: beta = 0.07, SE = 0.04, P = 0.04). Genetically predicted Vit-D and PTH showed no association with the traits, while FGF23 was inversely associated with SBP (IVW: beta = -0.11, SE = 0.04, P = 0.01), although this association lost statistical significance in sensitivity analysis.
Our study shows a direct association between genetically predicted calcium level and DBP, and a weaker association with SBP. No such clear association was found for genetically predicted calciotropic hormone levels. It is of interest to detect which target genes involved in calcium homeostasis mediate the effect of calcium on BP, particularly for improving personalized intervention strategies.
摘要：
维生素D（Vit-D），甲状旁腺激素（PTH），和成纤维细胞生长因子23（FGF23）是主要的钙激素参与调节来自肠道的血钙水平，肾,和骨骼通过紧密的内分泌反馈循环系统。改变钙本身的水平或通过其调节激素的作用可能会影响血压（BP），但确切的机制尚不清楚。
为了评估血清钙水平和/或与血压稳态有关的调节激素之间是否存在因果关系，我们进行了双样本孟德尔随机化(MR)研究.
从4个大型全基因组关联研究（GWAS）中，我们获得了与血清钙（119个SNP）相关的独立（r2<0.001）单核苷酸多态性（SNP），Vit-D（78个SNP），PTH（5个SNP），和FGF23（5个SNP），在瑞典城市研究中，通过MR研究它们与收缩压血压（SBP）和舒张压血压（DBP）的关系，马尔默饮食与癌症研究(n=29298)。因果关系采用逆方差加权法(IVW)和加权中位数进行评估，而MREgger和MR-PRESSO用作敏感性分析。
遗传预测的血清钙水平与DBP（IVW：β=0.10，SE=0.04，P=0.007）和SBP（IVW：β=0.07，SE=0.04，P=0.04）相关。遗传预测的Vit-D和PTH与性状没有相关性，而FGF23与SBP呈负相关(IVW:β=-0.11,SE=0.04,P=0.01),尽管这种关联在敏感性分析中失去了统计学意义.
我们的研究表明，基因预测的钙水平与DBP之间存在直接关联，与SBP的联系较弱。对于遗传预测的钙化激素水平，没有发现如此明确的关联。感兴趣的是检测参与钙稳态的靶基因介导钙对BP的影响。特别是改进个性化干预策略。
为了评估血清钙水平和/或与血压稳态有关的调节激素之间是否存在因果关系，我们进行了双样本孟德尔随机化(MR)研究.
从4个大型全基因组关联研究（GWAS）中，我们获得了与血清钙（119个SNP）相关的独立（r2<0.001）单核苷酸多态性（SNP），Vit-D（78个SNP），PTH（5个SNP），和FGF23（5个SNP），在瑞典城市研究中，通过MR研究它们与收缩压血压（SBP）和舒张压血压（DBP）的关系，马尔默饮食与癌症研究(n=29298)。因果关系采用逆方差加权法(IVW)和加权中位数进行评估，而MREgger和MR-PRESSO用作敏感性分析。
遗传预测的血清钙水平与DBP（IVW：β=0.10，SE=0.04，P=0.007）和SBP（IVW：β=0.07，SE=0.04，P=0.04）相关。遗传预测的Vit-D和PTH与性状没有相关性，而FGF23与SBP呈负相关(IVW:β=-0.11,SE=0.04,P=0.01),尽管这种关联在敏感性分析中失去了统计学意义.
我们的研究表明，基因预测的钙水平与DBP之间存在直接关联，与SBP的联系较弱。对于遗传预测的钙化激素水平，没有发现如此明确的关联。感兴趣的是检测参与钙稳态的靶基因介导钙对BP的影响。特别是改进个性化干预策略。
