Genetic insights into the relationship between circulating immune cell and pancreatic ductal adenocarcinoma:a Mendelian randomization analysis
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NETL
NSTL
万方数据
目的:使用双样本孟德尔随机化分析方法,辨别389种免疫细胞表型与胰腺导管腺癌(PDAC)风险之间的遗传学相关性.方法:从目前已公开发表的全基因组关联研究中获取389种免疫细胞和PDAC的全基因组关联研究(GWAS)数据,使用逆方差加权(IVW)作为主要分析方法,并进行敏感性分析验证结果的可靠性,以辨别不同免疫细胞特征与PDAC风险之间的遗传相关性.结果:B细胞和T淋巴细胞,以及其他免疫细胞类型,对PDAC风险有双向影响.所有髓细胞对PDAC均显示有保护作用,OR值和95％置信区间(95％CI)均小于 1.此外,记忆 B 细胞上的 CD20(OR=0.798,95％CI0.655～0.972,P=0.025)、IgD-CD38-B 细胞上的 CD19(OR=0.780,95％CI0.625～0.975,P=0.029)、单核细胞上的 CD64(OR=0.888,95％CI 0.800～0.985,P=0.024)、CD8+CD28-Treg 上的 CD8(OR=0.724,95％CI0.569～0.920,P=0.008)和自然杀伤 T 细胞(NKT)细胞上的 CD45(OR=0.826,95％CI 0.711～0.958,P=0.012)对 PDAC 显示有显著的保护作用.经异质性及敏感性检验,关联结果被确定为稳定的.结论:本研究为免疫细胞与PDAC之间的关联提供了新的遗传学思路,强调了免疫细胞在PDAC发病机制中的复杂作用,同时为探索PDAC的发病机制和免疫治疗提供了一定的理论支持.
Objective:To discern genetic correlations between 389 immune cell phenotypes and risk of pancreatic ductal adenocarcinoma(PDAC)using two-sample Mendelian randomization analysis.Methods:Genome-wide association study(GW AS)data on 389 immune cells and PDAC were obtained from currently published genome-wide association studies.Inverse variance weighting(IVW)was used as the primary analysis method and sensitivity analyses were performed to validate the reliability of the results,in order to discern the genetic correlation between different immune cell traits and the risk of PDAC.Results:B-cells and T-lymphocytes,as well as other immune cell types,had bidirectional effects on PDAC risk.Notably,all myeloid cells showed a protective effect against PDAC,with ORs and 95％confidence intervals(95％CI)less than 1.In addition,CD20 on memory B cells(OR=0.798,95％CIO.655-0.972,P=0.025),CD19 on IgD-CD38-B cells(OR=0.780,95％CI0.625-0.975,P=0.029),CD64 on monocytes(OR=0.888,95％CI 0.800-0.985,P=0.024),CD8 on CD8+CD28-Treg(OR=0.724,95％CI 0.569-0.920,P=0.008)and CD45 on NKT cells(OR=0.826,95％CI0.711-0.958,P=0.012)showed significant protection against PDAC.Finally,the association results were confirmed to be stable after heterogeneity and sensitivity tests.Conclusion:This study provides new genetic insights into the association between immune cells and PDAC,emphasizing the complex role of immune cells in the pathogenesis of PDAC,which provides some theoretical support for basic research to explore the pathogenesis and immunotherapy of PDAC.
NETL
NSTL
万方数据
