Zhao Qiuping, Liu Rongmei, Chen Hui, Yang Xiaomo, Dong Jiajia, Bai Minfu
Fuwai Central China Cardiovascular Hospital, Heart Center of Henan Provincial People's Hospital, Zhengzhou, China.
Front Genet. 2023 Feb 7;14:1127820. doi: 10.3389/fgene.2023.1127820. eCollection 2023.
The causal direction and magnitude of the associations between blood cell count and coronary heart disease (CHD) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between blood cell count and CHD using Mendelian randomization (MR). In this two-sample MR study, we identified independent blood cell count associated genetic variants from a genome-wide association studies (GWAS) among European ancestry individuals. Summary level data of CHD was obtained from a GWAS consisting of 547261 subjects. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and outlier test (MR-PRESSO) were conducted to investigate the associations between blood cell and CHD. Among all cardiovascular outcomes of interest, blood cell counts were only associated with CHD. Our findings indicated that white blood cell count and neutrophil cell count were significantly associated with increased risk of CHD [odds ratio (OR) = 1.07, 95% confidence interval (CI), 1.01-1.14; OR = 1.09, 1.02-1.16). However, there was no significant association between monocyte cell count, basophil cell count, lymphocyte cell count, eosinophil cell count, and CHD ( > 0.05). The results after excluding outliers were consistent with main results and the sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, > 0.05). Our MR study suggested that greater white blood cell count and neutrophil cell count were associated with a higher risk of CHD. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.
由于存在反向因果关系和混杂因素的影响，血细胞计数与冠心病（CHD）之间关联的因果方向和程度仍不明确。本研究旨在采用孟德尔随机化（MR）方法探讨血细胞计数与冠心病之间的关联。在这项两样本MR研究中，我们从欧洲血统个体的全基因组关联研究（GWAS）中确定了与血细胞计数相关的独立基因变异。冠心病的汇总水平数据来自一项包含547261名受试者的GWAS。采用逆方差加权（IVW）、孟德尔随机化Egger（MR-Egger）、加权中位数和离群值检验（MR-PRESSO）方法来研究血细胞与冠心病之间的关联。在所有感兴趣的心血管结局中，血细胞计数仅与冠心病相关。我们的研究结果表明，白细胞计数和中性粒细胞计数与冠心病风险增加显著相关[比值比（OR）=1.07，95%置信区间（CI），1.01-1.14；OR =1.09，1.02-1.16]。然而，单核细胞计数、嗜碱性粒细胞计数、淋巴细胞计数、嗜酸性粒细胞计数与冠心病之间无显著关联（>0.05）。排除离群值后的结果与主要结果一致，敏感性分析未显示多效性证据（MR-Egger截距，>0.05）。我们的MR研究表明，较高的白细胞计数和中性粒细胞计数与较高的冠心病风险相关。未来仍需开展研究以验证这些结果并探究这些关联背后的机制。
