PDF(Pubmed)
Abstract：
UNASSIGNED: Ankylosing spondylitis (AS) is an autoimmune disease that affects millions of individuals. Immune cells have been recognized as having a crucial role in the pathogenesis of AS. However, their relationship has not been fully explored.
UNASSIGNED: We chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran\'s Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells.
UNASSIGNED: Overall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p < 6.84E-05. CD8 on effector memory CD8+ T cell could increase the risk of AS (p: 1.2302E-05, OR: 2.9871, 95%CI: 1.8289-4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E-06, OR: 0.5446, 95%CI: 0.4260-0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E-06, OR: 0.0.5423, 95%CI: 0.4210-0.6983). Our findings were consistently stable and reliable.
UNASSIGNED: Our findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration.
UNASSIGNED: We chose to employ Mendelian randomization (MR) to investigate the potential correlation between immune cells and AS. We sourced the data on immune cells from the latest genome-wide association studies (GWASs). We obtained data on AS from the FinnGen consortium. Our comprehensive univariable MR analysis covered 731 immune cells to explore its potential causal relationship with AS. The primary analysis method was inverse-variance weighted (IVW). Additionally, we used Cochran\'s Q test and the MR-Egger intercept test to assess the presence of pleiotropy and heterogeneity. We examined whether our results could be influenced by individual single-nucleotide polymorphisms (SNPs) using the leave-one-out test. We conducted a bidirectional MR to investigate the reverse relationship. We also applied multivariable MR to decrease the potential influence between the immune cells.
UNASSIGNED: Overall, our univariable MR analysis revealed eight immune cells associated with AS. Among these, four immune cells contributed to an increased risk of AS, while four immune cells were identified as protective factors for AS. However, the Bonferroni test confirmed only one risk factor and one protective factor with a significance level of p < 6.84E-05. CD8 on effector memory CD8+ T cell could increase the risk of AS (p: 1.2302E-05, OR: 2.9871, 95%CI: 1.8289-4.8786). HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 1.2301E-06, OR: 0.5446, 95%CI: 0.4260-0.6962). We also identified a bidirectional relationship between CD4 on CD39+ activated CD4 regulatory T cells and AS utilizing the bidirectional MR. To address potential confounding among immune cells, we employed multivariable MR analysis, which revealed that only one immune cell had an independent effect on AS. HLA DR on CD33dim HLA DR+ CD11b+ could decrease the risk of AS (p: 2.113E-06, OR: 0.0.5423, 95%CI: 0.4210-0.6983). Our findings were consistently stable and reliable.
UNASSIGNED: Our findings indicated a potential link between immune cells and AS, which could provide a new idea for future research. Nevertheless, the specific underlying mechanisms require further exploration.
摘要：
强直性脊柱炎（AS）是一种自身免疫性疾病，影响数百万人。免疫细胞已被认为在AS的发病机理中起着至关重要的作用。然而,他们的关系还没有得到充分的探索。
■我们选择采用孟德尔随机化(MR)来研究免疫细胞与AS之间的潜在相关性。我们从最新的全基因组关联研究（GWAS）中获取了免疫细胞的数据。我们从FinnGen联盟获得了AS的数据。我们全面的单变量MR分析涵盖了731个免疫细胞，以探讨其与AS的潜在因果关系。主要分析方法为逆方差加权(IVW)。此外,我们使用Cochran的Q检验和MR-Egger截距检验来评估多效性和异质性的存在。我们使用留一法检验了我们的结果是否会受到单个单核苷酸多态性（SNP）的影响。我们进行了双向MR以研究反向关系。我们还应用多变量MR来降低免疫细胞之间的潜在影响。
■总的来说，我们的单变量MR分析显示8个与AS相关的免疫细胞.其中,四种免疫细胞增加了AS的风险，而四种免疫细胞被鉴定为AS的保护因子。然而,Bonferroni检验仅证实了一个危险因素和一个保护因素，其显著性水平为p<6.84E-05。效应记忆CD8+T细胞上的CD8可增加AS的风险(p:1.2302E-05,OR:2.9871,95CI:1.8289-4.8786)。CD33dimHLADR+CD11b+可以降低AS的风险（p：1.2301E-06，OR：0.5446，95CI：0.4260-0.6962）。我们还利用双向MR鉴定了CD39激活的CD4调节性T细胞上的CD4与AS之间的双向关系。为了解决免疫细胞之间潜在的混杂问题，我们采用了多变量MR分析，这表明只有一个免疫细胞对AS有独立的作用。CD33dimHLADR+CD11b+可以降低AS的风险（p：2.113E-06，OR：0.0.5323，95CI：0.4210-0.6983）。我们的研究结果始终稳定可靠。
■我们的研究结果表明，免疫细胞和AS之间存在潜在的联系，这可以为未来的研究提供新的思路。然而，具体的基础机制需要进一步探索。
■我们选择采用孟德尔随机化(MR)来研究免疫细胞与AS之间的潜在相关性。我们从最新的全基因组关联研究（GWAS）中获取了免疫细胞的数据。我们从FinnGen联盟获得了AS的数据。我们全面的单变量MR分析涵盖了731个免疫细胞，以探讨其与AS的潜在因果关系。主要分析方法为逆方差加权(IVW)。此外,我们使用Cochran的Q检验和MR-Egger截距检验来评估多效性和异质性的存在。我们使用留一法检验了我们的结果是否会受到单个单核苷酸多态性（SNP）的影响。我们进行了双向MR以研究反向关系。我们还应用多变量MR来降低免疫细胞之间的潜在影响。
■总的来说，我们的单变量MR分析显示8个与AS相关的免疫细胞.其中,四种免疫细胞增加了AS的风险，而四种免疫细胞被鉴定为AS的保护因子。然而,Bonferroni检验仅证实了一个危险因素和一个保护因素，其显著性水平为p<6.84E-05。效应记忆CD8+T细胞上的CD8可增加AS的风险(p:1.2302E-05,OR:2.9871,95CI:1.8289-4.8786)。CD33dimHLADR+CD11b+可以降低AS的风险（p：1.2301E-06，OR：0.5446，95CI：0.4260-0.6962）。我们还利用双向MR鉴定了CD39激活的CD4调节性T细胞上的CD4与AS之间的双向关系。为了解决免疫细胞之间潜在的混杂问题，我们采用了多变量MR分析，这表明只有一个免疫细胞对AS有独立的作用。CD33dimHLADR+CD11b+可以降低AS的风险（p：2.113E-06，OR：0.0.5323，95CI：0.4210-0.6983）。我们的研究结果始终稳定可靠。
■我们的研究结果表明，免疫细胞和AS之间存在潜在的联系，这可以为未来的研究提供新的思路。然而，具体的基础机制需要进一步探索。
