PDF(Pubmed)
Abstract：
UNASSIGNED: Allergic rhinitis (AR), a prevalent chronic inflammatory condition triggered by immunoglobulin E (IgE), involves pivotal roles of immune and metabolic factors in its onset and progression. However, the intricacies and uncertainties in clinical research render current investigations into their interplay somewhat inadequate.
UNASSIGNED: To elucidate the causal relationships between immune cells, metabolites, and AR, we conducted a mediation Mendelian randomization (MR) analysis.
UNASSIGNED: Leveraging comprehensive publicly accessible summary-level data from genome-wide association studies (GWAS), this study employed the two-sample MR research method to investigate causal relationships among 731 immune cell phenotypes, 1400 metabolite levels, and AR. Additionally, employing the mediation MR approach, the study analyzed potential mediated effect of metabolites in the relationships between immune cells and AR. Various sensitivity analysis methods were systematically employed to ensure the robustness of the results.
UNASSIGNED: Following false discovery rate (FDR) correction, we identified three immune cell phenotypes as protective factors for AR: Naive CD8br %CD8br (odds ratio (OR): 0.978, 95% CI = 0.966-0.990, P = 4.5×10-4), CD3 on CD39+ activated Treg (OR: 0.947, 95% CI = 0.923-0.972, P = 3×10-5), HVEM on CD45RA- CD4+ (OR: 0.967, 95% CI = 0.948-0.986, P = 4×10-5). Additionally, three metabolite levels were identified as risk factors for AR: N-methylhydroxyproline levels (OR: 1.219, 95% CI = 1.104-1.346, P = 9×10-5), N-acetylneuraminate levels (OR: 1.133, 95% CI = 1.061-1.211, P = 1.7×10-4), 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4) levels (OR: 1.058, 95% CI = 1.029-1.087, P = 5×10-5). Mediation MR analysis indicated a causal relationship between Naive CD8br %CD8br and N-methylhydroxyproline levels, acting as a protective factor (OR: 0.971, 95% CI = 0.950-0.992, P = 8.31×10-3). The mediated effect was -0.00574, accounting for 26.1% of the total effect, with a direct effect of -0.01626. Naive CD8+ T cells exert a protective effect on AR by reducing N-methylhydroxyproline levels.
UNASSIGNED: Our study, delving into genetic information, has substantiated the intricate connection between immune cell phenotypes and metabolite levels with AR. This reveals a potential pathway to prevent the onset of AR, providing guiding directions for future clinical investigations.
UNASSIGNED: To elucidate the causal relationships between immune cells, metabolites, and AR, we conducted a mediation Mendelian randomization (MR) analysis.
UNASSIGNED: Leveraging comprehensive publicly accessible summary-level data from genome-wide association studies (GWAS), this study employed the two-sample MR research method to investigate causal relationships among 731 immune cell phenotypes, 1400 metabolite levels, and AR. Additionally, employing the mediation MR approach, the study analyzed potential mediated effect of metabolites in the relationships between immune cells and AR. Various sensitivity analysis methods were systematically employed to ensure the robustness of the results.
UNASSIGNED: Following false discovery rate (FDR) correction, we identified three immune cell phenotypes as protective factors for AR: Naive CD8br %CD8br (odds ratio (OR): 0.978, 95% CI = 0.966-0.990, P = 4.5×10-4), CD3 on CD39+ activated Treg (OR: 0.947, 95% CI = 0.923-0.972, P = 3×10-5), HVEM on CD45RA- CD4+ (OR: 0.967, 95% CI = 0.948-0.986, P = 4×10-5). Additionally, three metabolite levels were identified as risk factors for AR: N-methylhydroxyproline levels (OR: 1.219, 95% CI = 1.104-1.346, P = 9×10-5), N-acetylneuraminate levels (OR: 1.133, 95% CI = 1.061-1.211, P = 1.7×10-4), 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4) levels (OR: 1.058, 95% CI = 1.029-1.087, P = 5×10-5). Mediation MR analysis indicated a causal relationship between Naive CD8br %CD8br and N-methylhydroxyproline levels, acting as a protective factor (OR: 0.971, 95% CI = 0.950-0.992, P = 8.31×10-3). The mediated effect was -0.00574, accounting for 26.1% of the total effect, with a direct effect of -0.01626. Naive CD8+ T cells exert a protective effect on AR by reducing N-methylhydroxyproline levels.
UNASSIGNED: Our study, delving into genetic information, has substantiated the intricate connection between immune cell phenotypes and metabolite levels with AR. This reveals a potential pathway to prevent the onset of AR, providing guiding directions for future clinical investigations.
摘要：
■过敏性鼻炎（AR），由免疫球蛋白E（IgE）引发的普遍慢性炎症，涉及免疫和代谢因子在其发病和进展中的关键作用。然而,临床研究的复杂性和不确定性使得目前对其相互作用的研究有些不足.
■为了阐明免疫细胞之间的因果关系，代谢物，AR,我们进行了调解孟德尔随机化(MR)分析.
■利用来自全基因组关联研究（GWAS）的可公开获取的综合汇总数据，本研究采用双样本MR研究方法研究了731种免疫细胞表型之间的因果关系，1400个代谢物水平，和AR。此外,采用调解MR方法，该研究分析了代谢产物在免疫细胞与AR之间关系中的潜在介导作用。系统地采用了各种灵敏度分析方法来确保结果的稳健性。
■错误发现率(FDR)校正后，我们确定了三种免疫细胞表型作为AR的保护因子：幼稚CD8br%CD8br（比值比（OR）：0.978，95％CI=0.966-0.990，P=4.5×10-4），CD39+激活的Treg上的CD3(OR:0.947,95%CI=0.923-0.972,P=3×10-5),HVEM对CD45RA-CD4+的影响(OR:0.967,95%CI=0.948-0.986,P=4×10-5)。此外,三种代谢物水平被确定为AR的危险因素:N-甲基羟脯氨酸水平(OR:1.219,95%CI=1.104-1.346,P=9×10-5),N-乙酰神经氨酸水平（OR：1.133，95％CI=1.061-1.211，P=1.7×10-4），1-硬脂酰-2-花生四酰基-gpc(18:0/20:4)水平(OR:1.058,95%CI=1.029-1.087,P=5×10-5)。中介MR分析表明，幼稚CD8br%CD8br和N-甲基羟脯氨酸水平之间存在因果关系，作为保护因素(OR:0.971,95%CI=0.950~0.992,P=8.31×10-3)。介导效应为-0.00574,占总效应的26.1%,直接效应为-0.01626。幼稚CD8+T细胞通过降低N-甲基羟脯氨酸水平发挥对AR的保护作用。
■我们的研究，深入研究遗传信息，证实了免疫细胞表型和AR代谢物水平之间的复杂联系。这揭示了预防AR发作的潜在途径，为未来的临床研究提供指导方向。
■为了阐明免疫细胞之间的因果关系，代谢物，AR,我们进行了调解孟德尔随机化(MR)分析.
■利用来自全基因组关联研究（GWAS）的可公开获取的综合汇总数据，本研究采用双样本MR研究方法研究了731种免疫细胞表型之间的因果关系，1400个代谢物水平，和AR。此外,采用调解MR方法，该研究分析了代谢产物在免疫细胞与AR之间关系中的潜在介导作用。系统地采用了各种灵敏度分析方法来确保结果的稳健性。
■错误发现率(FDR)校正后，我们确定了三种免疫细胞表型作为AR的保护因子：幼稚CD8br%CD8br（比值比（OR）：0.978，95％CI=0.966-0.990，P=4.5×10-4），CD39+激活的Treg上的CD3(OR:0.947,95%CI=0.923-0.972,P=3×10-5),HVEM对CD45RA-CD4+的影响(OR:0.967,95%CI=0.948-0.986,P=4×10-5)。此外,三种代谢物水平被确定为AR的危险因素:N-甲基羟脯氨酸水平(OR:1.219,95%CI=1.104-1.346,P=9×10-5),N-乙酰神经氨酸水平（OR：1.133，95％CI=1.061-1.211，P=1.7×10-4），1-硬脂酰-2-花生四酰基-gpc(18:0/20:4)水平(OR:1.058,95%CI=1.029-1.087,P=5×10-5)。中介MR分析表明，幼稚CD8br%CD8br和N-甲基羟脯氨酸水平之间存在因果关系，作为保护因素(OR:0.971,95%CI=0.950~0.992,P=8.31×10-3)。介导效应为-0.00574,占总效应的26.1%,直接效应为-0.01626。幼稚CD8+T细胞通过降低N-甲基羟脯氨酸水平发挥对AR的保护作用。
■我们的研究，深入研究遗传信息，证实了免疫细胞表型和AR代谢物水平之间的复杂联系。这揭示了预防AR发作的潜在途径，为未来的临床研究提供指导方向。
