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. 2024 Oct 31:15:1444753.
doi: 10.3389/fneur.2024.1444753. eCollection 2024.

Associations between T-cell traits and narcolepsy type 1: new insights from a Mendelian randomization study

Shiqin Chen #  1 , Tian Lv #  2 , Zongshan Li #  3 , Gonghua Pan #  1 , Yiqiao Chen  4 , Xingwang Zhao  5 , Lisan Zhang  6
Affiliations

Associations between T-cell traits and narcolepsy type 1: new insights from a Mendelian randomization study

Shiqin Chen et al. Front Neurol. .

Abstract

Background: Narcolepsy type 1 (NT1) is primarily caused by a malfunctioning immune system in which T-cells damage the hypothalamus. To elucidate the causal relationships between biomarkers in T-cells and NT1, we employed Mendelian randomization (MR) analysis.

Methods: We conducted a two-sample MR analysis utilizing genetically predicted T-cell traits to examine their effects on NT1. Genome-wide association study summary data were extracted from studies by Valeria (3,757 participants) for 211 T-cell traits, Ollila (6,073 cases and 84,856 controls) for NT1. The MR analysis was executed at two threshold levels. Inverse variance weighted, Wald ratio, weighted median, and MR-Egger regression methods were used for the MR analysis. Odds ratios (ORs) were calculated, and heterogeneity tests, as well as pleiotropy tests, were conducted.

Results: After Bonferroni correction at the significant level (p < 1.18 × 10-4), a higher ratio of naive CD4- CD8- T-cells was identified as a risk factor for NT1 (OR = 10.50; 95% CI: 6.98, 15.90, p = 3.89 ×10-29). Conversely, CD4 on HLA DR+ CD4+ T cells (mean fluorescence intensity, MFI) exhibited a negative correlation with NT1. At nominally significant levels (p < 0.05) for both threshold levels, HVEM (herpesvirus entry mediator) on naive CD8+ T cells (MFI) was suggested as a protective factor for NT1. Additionally, a higher ratio of CD25++ CD45RA- CD4 not regulatory T cells, CD127 on CD45RA- CD4 not regulatory T cells (MFI), CD127 on CD28+ CD4+ T cells (MFI), CD3 on HLA DR+ T cells (MFI), and CD3 on HLA DR+ CD4+ T cells (MFI) were suggested as risk factors for NT1.

Conclusion: This study confirmed the causal effects of CD4+ and CD8+ T-cells on NT1 and found several novel T-cell-related characteristics.

Keywords: CD4− CD8− T-cells; Mendelian randomization; T-cells; herpesvirus entry mediator; narcolepsy type 1.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Study design schematic.
Figure 2
Figure 2
Primary Mendelian randomization analysis results at 5 × 10−8 SNP selection threshold.
Figure 3
Figure 3
Primary Mendelian randomization analysis results at 5 × 10−6 SNP selection threshold.
See this image and copyright information in PMC

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