C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study.
C-Reactive Protein Levels and Risk of Cardiovascular Diseases: A Two-Sample Bidirectional Mendelian Randomization Study.
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DOI：
10.3390/ijms24119129
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发表时间：
2023-05-23
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
C反应蛋白（CRP）水平升高是炎症的指标，是心血管疾病（CVD）的主要危险因素。然而，观察性研究中的这种潜在相关性仍不确定。我们进行了一项双样本双向孟德尔随机化（MR）研究，使用公开可用的GWAS汇总统计量来评估CRP和CVD之间的关系。工具变量（IV）被仔细选择，并使用多种方法来得出可靠的结论。采用MR-Egger截距和Cochran's Q检验评价水平多效性和异质性。使用F统计量确定IV的强度。CRP对高血压性心脏病（HHD）风险的因果作用具有统计学意义，但我们没有观察到CRP与心肌梗死、冠状动脉疾病、心力衰竭或动脉粥样硬化风险之间存在显著的因果关系。我们的初步分析，在使用MR-MOVO和多变量MR方法进行离群值校正后，显示增加CRP水平的IV也增加了HHD风险。然而，在排除使用PhenoScanner识别的离群IV后，初始MR结果发生了变化，但敏感性分析仍与主要分析的结果一致。我们没有发现CVD和CRP之间反向因果关系的证据。我们的研究结果需要更新MR研究，以确认CRP作为HHD临床生物标志物的作用。
Elevated C-reactive protein (CRP) levels are an indicator of inflammation, a major risk factor for cardiovascular disease (CVD). However, this potential association in observational studies remains inconclusive. We performed a two-sample bidirectional Mendelian randomization (MR) study using publicly available GWAS summary statistics to evaluate the relationship between CRP and CVD. Instrumental variables (IVs) were carefully selected, and multiple approaches were used to make robust conclusions. Horizontal pleiotropy and heterogeneity were evaluated using the MR-Egger intercept and Cochran’s Q-test. The strength of the IVs was determined using F-statistics. The causal effect of CRP on the risk of hypertensive heart disease (HHD) was statistically significant, but we did not observe a significant causal relationship between CRP and the risk of myocardial infarction, coronary artery disease, heart failure, or atherosclerosis. Our primary analyses, after performing outlier correction using MR-PRESSO and the Multivariable MR method, revealed that IVs that increased CRP levels also increased the HHD risk. However, after excluding outlier IVs identified using PhenoScanner, the initial MR results were altered, but the sensitivity analyses remained congruent with the results from the primary analyses. We found no evidence of reverse causation between CVD and CRP. Our findings warrant updated MR studies to confirm the role of CRP as a clinical biomarker for HHD.
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影响因子：
7.7
作者：
Bowden J;Del Greco M F;Minelli C;Davey Smith G;Sheehan NA;Thompson JR
通讯作者：
Thompson JR
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
5.6
作者：
Jebari-Benslaiman S;Galicia-García U;Larrea-Sebal A;Olaetxea JR;Alloza I;Vandenbroeck K;Benito-Vicente A;Martín C
通讯作者：
Martín C
影响因子：
5.8
作者：
Kamat, Mihir A.;Blackshaw, James A.;Staley, James R.
通讯作者：
Staley, James R.