State Key Laboratory of Respiratory Disease, Department of Otolaryngology-Head and Neck Surgery, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
Neurol Sci. 2022 Sep;43(9):5575-5580. doi: 10.1007/s10072-022-06123-7. Epub 2022 May 12.
Blood cell properties effectively reflect immune status. Basophil and CD8 CD27 T cell levels are correlated with narcolepsy, but their causal association is unclear. This study aims to evaluate the causality between blood cell count and narcolepsy risk at the genetic level.
Two-sample Mendelian randomization (MR) analyses were performed on 35 published blood cell properties, using genome-wide association study (GWAS) datasets and one published GWAS dataset of narcolepsy, to explore causality between blood cell count and narcolepsy risk. Inverse variance weighted, MR-Egger, and weighted median approaches were employed for the MR analysis, odds ratio (OR) calculations, and heterogeneity tests of single nucleotide polymorphisms were conducted with the TwoSampleMR package in R. Multivariable Mendelian randomization (MVMR) was used to adjust the analysis further and eliminate the mediation effect between exposures.
Basophil counts, total basophil neutrophil counts, total neutrophil eosinophil counts, granulocyte counts, and myeloid white cell counts showed inverse associations with narcolepsy risk based on the two-sample MR analysis. MVMR confirmed that only basophil counts were significantly associated with narcolepsy risk for the blood cell properties tested (OR = 0.23, 95% confidence interval 0.08-0.62; p = 0.004, power = 99.99%). Each standard deviation increase in basophil count (0.03 per nL), compared to the median level (0.04 per nL), decreased narcolepsy risk by 77%.
Higher white blood cell counts, especially basophil counts, are protective factors for narcolepsy. Basophil counts has great potential to be used as a new biomarker to shorten diagnostic delay and to monitor the therapeutic effects of treatments for narcolepsy.
血细胞特性能有效反映免疫状态。嗜碱性粒细胞和 CD8 CD27 T 细胞水平与嗜睡症相关，但它们之间的因果关联尚不清楚。本研究旨在从遗传水平评估血细胞计数与嗜睡症风险之间的因果关系。
利用全基因组关联研究（GWAS）数据集和一项已发表的嗜睡症 GWAS 数据集，对 35 种已发表的血细胞特性进行两样本孟德尔随机化（MR）分析，以探讨血细胞计数与嗜睡症风险之间的因果关系。采用逆方差加权、MR-Egger 和加权中位数方法进行 MR 分析，使用 R 语言中的 TwoSampleMR 包计算比值比（OR）和单核苷酸多态性的异质性检验。多变量孟德尔随机化（MVMR）用于进一步调整分析并消除暴露因素之间的中介效应。
基于两样本 MR 分析，嗜碱性粒细胞计数、总嗜碱性粒细胞中性粒细胞计数、总中性粒细胞嗜酸性粒细胞计数、粒细胞计数和髓样白细胞计数与嗜睡症风险呈负相关。MVMR 证实，在所测试的血细胞特性中，只有嗜碱性粒细胞计数与嗜睡症风险显著相关（OR=0.23，95%置信区间 0.08-0.62；p=0.004，效能=99.99%）。与中位数水平（0.04 皮升）相比，嗜碱性粒细胞计数每增加一个标准差（0.03 皮升），嗜睡症风险降低 77%。
较高的白细胞计数，尤其是嗜碱性粒细胞计数，是嗜睡症的保护因素。嗜碱性粒细胞计数极有可能成为一种新的生物标志物，用于缩短诊断延迟，并监测嗜睡症的治疗效果。
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