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. 2022 Sep;43(9):5575-5580.
doi: 10.1007/s10072-022-06123-7. Epub 2022 May 12.

Higher basophil count decreases narcolepsy risk: a Mendelian randomization study

Ang Li  1 , Hao Li  1 , Junyang Xie  1 , Jianlei Xie  1 , Wenjing Liao  1 , Lijuan Song  1 , Xiaowen Zhang  2
Affiliations

Higher basophil count decreases narcolepsy risk: a Mendelian randomization study

Ang Li et al. Neurol Sci. 2022 Sep.

Abstract

Background: 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.

Methods: 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.

Results: 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%.

Conclusion: 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.

Keywords: Basophil count; Causality; Mendelian randomization; Narcolepsy; Protective factor.

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