Causal Inference of Carnitine on Blood Pressure and potential mediation by uric acid: A mendelian randomization analysis.
Causal Inference of Carnitine on Blood Pressure and potential mediation by uric acid: A mendelian randomization analysis.
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DOI：
10.1016/j.ijcrp.2021.200120
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发表时间：
2021-12
期刊：
影响因子：
--
通讯作者：
Zachariah JP
中科院分区：
文献类型：
--
作者：
Richard MA;Lupo PJ;Zachariah JP
饮食变化会改变血压（BP），但具体的饮食因素尚不清楚。鉴于先前的观察数据表明血清肉碱或尿酸影响血压，我们研究了血清肉碱和血清尿酸浓度对血压的作用，并使用两样本双向孟德尔随机化 (MR) 分析考虑了脂质和胰岛素抵抗的调节。我们进行了 MR 来表征肉碱或尿酸对心脏代谢特征的双向因果关系。我们使用来自肉碱、尿酸、血压、血脂和血糖特征的单独大规模基因组分析的全基因组关联汇总数据进行了两样本 MR。我们使用逆方差加权 (IVW) 荟萃分析和 MR Egger 回归来分别测试不存在和存在多效性的情况下的因果关系，并进行敏感性分析以识别混杂因素和中间因素。在我们的分析中，肉碱与收缩压直接因果相关（IVW 效应 = 0.2，因果 p 值 = 0.03），但与舒张压无关（IVW 因果 p = 0.1）。我们的研究结果还支持肉碱与甘油三酯和尿酸的直接和间接关系。没有发现肉碱与血糖特征之间存在因果关系。尿酸与血压和甘油三酯均无关。两个样本的双向 MR 证明肉碱（而非尿酸）对收缩压而非舒张压具有无混杂的因果效应，表明肉碱在动脉僵硬度中发挥作用。肉碱（但尿酸除外）对 TG 也有直接和间接影响，但与肉碱对收缩压的因果作用无关。
Dietary change alters blood pressure (BP) but the specific causal dietary elements are unclear. Given previous observational data suggesting serum carnitine or uric acid affect BP, we investigated the role of serum carnitine and serum uric acid concentrations on BP, and considered mediation by lipids and insulin resistance using two-sample bi-directional Mendelian randomization (MR) analysis. We performed MR to characterize bi-directional causal relationships of carnitine or uric acid on cardiometabolic traits. We performed two-sample MR using genome-wide association summary data from separate large-scale genomic analyses of carnitine, uric acid, BP, lipids, and glycemic traits. We used inverse variance weighted (IVW) meta-analysis and MR Egger regression to test for causal relations in the absence and presence of pleiotropy, respectively, and performed sensitivity analyses to identify confounders and intermediates. In our analysis, carnitine was directly, causally associated with systolic BP (IVW effect = 0.2, causal p-value = 0.03) but not diastolic BP (IVW causal p = 0.1). Our findings additionally support direct and indirect relationships of carnitine on TG and on uric acid. No causal associations of carnitine were found with glycemic traits. Uric acid was not associated with BP, nor TG. Two-sample bi-directional MR demonstrated an unconfounded causal effect of carnitine, but not uric acid, on systolic but not diastolic BP, suggesting a role of carnitine in arterial stiffness. Carnitine, but not uric acid, also has direct and indirect effects on TG but are independent of the causal effect of carnitine on systolic BP.
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DOI：
10.1097/ede.0000000000000559
发表时间：
2017-01
期刊：
Epidemiology (Cambridge, Mass.)
影响因子：
--
作者：
Burgess S;Bowden J;Fall T;Ingelsson E;Thompson SG
通讯作者：
Thompson SG
影响因子：
5.9
作者：
Higuchi T;Abe M;Yamazaki T;Mizuno M;Okawa E;Ando H;Oikawa O;Okada K;Kikuchi F;Soma M
通讯作者：
Soma M
影响因子：
2.4
作者：
Koh, Angela S.;Gao, Fei;Kovalik, Jean-Paul
通讯作者：
Kovalik, Jean-Paul
影响因子：
7.7
作者：
Burgess, Stephen;Thompson, Simon G.
通讯作者：
Thompson, Simon G.
影响因子：
8.3
作者：
Mitchell, Gary F.;Conlin, Paul R.;Pfeffer, Marc A.
通讯作者：
Pfeffer, Marc A.