孟德尔随机化分析确定了循环 C 反应蛋白与脑出血之间的遗传因果关联。
Mendelian randomization analysis identifies a genetic casual association between circulating C-reactive protein and intracerebral hemorrhage.
机构信息
Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, PR China; West China Hospital, Sichuan University, Chengdu, PR China.
Clinical Laboratory, Boai Hospital of Zhongshan Affiliated to Southern Medical University, Zhongshan, PR China.
出版信息
J Stroke Cerebrovasc Dis. 2024 Feb;33(2):107554. doi: 10.1016/j.jstrokecerebrovasdis.2023.107554. Epub 2024 Jan 4.
BACKGROUND
The causal effect of C-reactive protein (CRP) on intracerebral hemorrhage (ICH) remains controversial. We discussed the causal association of CRP with ICH based on two-sample Mendelian randomization.
METHODS
The data from two genome-wide association studies (GWAS) of European ancestry was extracted, including circulating CRP levels (204,402 individuals) and ICH (1,687 cases and 201,146 controls). The inverse variance weighted (IVW) method was primary tool to evaluate the causal relationship of circulating CRP levels on ICH risk. MR-Egger regression and MR-PRESSO global test were utilized to identify pleiotropy. Heterogeneity was discussed with Cochran's Q test. The leave-one-out analysis explored the reliability of the results.
RESULTS
54 SNPs were identified as instrumental variables (IVs) for circulating CRP levels, and these IVs had no significant horizontal pleiotropy, heterogeneity, or bias. MR analysis demonstrated a causal relationship between elevated circulating CRP levels and decreased risk of ICH (OR = 0.828, 95% CI 0.692-0.992, P = 0.040).
CONCLUSION
Elevated circulating CRP levels demonstrated a significant potentially protective causal relationship with risk of ICH.
背景
C 反应蛋白（CRP）对脑出血（ICH）的因果效应仍存在争议。我们基于两样本 Mendelian 随机化探讨 CRP 与 ICH 的因果关联。
方法
从两个欧洲血统的全基因组关联研究（GWAS）中提取数据，包括循环 CRP 水平（204402 人）和 ICH（1687 例病例和 201146 例对照）。逆方差加权（IVW）法是评估循环 CRP 水平与 ICH 风险之间因果关系的主要工具。MR-Egger 回归和 MR-PRESSO 全局检验用于识别偏倚。MR 分析采用 Cochran's Q 检验探讨异质性。单样本剔除分析探讨结果的可靠性。
结果
确定了 54 个单核苷酸多态性（SNPs）作为循环 CRP 水平的工具变量（IVs），这些 IVs 无明显水平性偏倚、异质性或偏倚。MR 分析表明，循环 CRP 水平升高与 ICH 风险降低之间存在因果关系（OR=0.828，95%CI 0.692-0.992，P=0.040）。
结论
循环 CRP 水平升高与 ICH 风险之间存在显著的潜在保护因果关系。
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