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| 基于孟德尔随机化法的肠道菌群与额颞叶痴呆因果关联研究 |
| Causal Association Study of Gut Microbiome and Frontotemporal Dementia Based on Mendelian Randomization |
| 投稿时间：2025-05-17 修订日期：2025-05-17 |
| DOI： |
| 中文关键词: 肠道菌群 额颞叶痴呆 孟德尔随机化 |
| 英文关键词: Gut Microbiome, Frontotemporal Dementia, Mendelian Randomization |
| 基金项目: |
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| 摘要点击次数: 2 |
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| 中文摘要: |
| 【摘要】 目的 发现肠道菌群与额颞叶痴呆之间的潜在因果关系。方法 ：利用MiBioGen、IEU OpenGWAS project网站分别获取肠道菌群与额颞叶痴呆全基因组关联研究（GWAS）数据，选取与肠道菌群及额颞叶痴呆相关的遗传变异作为工具变量，分别采用MR分析的常用方法包括逆方差加权法（inverse variance weighted，IVW）、加权中位数法（weighted median，WME）、MR-Egger法、简单模式法（simple mode，SM）和加权模式法（weighted mode，WM）进行孟德尔随机化分析,最终通过逆方差加权法P值确定肠道菌群与额颞叶痴呆因果关系。同时采用Ｑ检验检验异质性， pleiotropy函数检验多效性。mrpresso检测水平基因多效性。Steiger检验方向性。结果 筛选出与额颞叶痴呆相关的遗传变异作为工具变量，瘤胃球菌与额颞叶痴呆之间存在因果关联（OR=0.134，95%CI：0.028~0.637，P<0.05），直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴呆之间存在因果关联（OR=10.672，95%CI：2.001~56.921，P<0. 05），异质性检验结果显示，瘤胃球菌、直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴呆的因果关联不存在异质性（P>0. 05）；水平多效性检验结果显示，瘤胃球菌、直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴呆的不存在水平多效性的影响（P>0. 05）；mrpresso检测水平基因多效性（P>0. 05）；steiger检验瘤胃球菌、直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴呆方向性（P＜0. 05）。结论 瘤胃球菌与额颞叶痴呆存在负向因果关系、直肠中梭菌属的Family_XIII_UCG_001与额颞叶痴呆存在正向因果关系。 |
| 英文摘要: |
| [Abstract] Purpose: Discovering the potential causal relationship between gut microbiota and frontotemporal dementia. Methods: Using MiBioGen and the IEU OpenGWAS project website obtain genome-wide association study (GWAS) data for gut microbiota and frontotemporal dementia, selecting genetic variants related to gut microbiota and frontotemporal dementia as instrumental variables. Mendelian randomization analysis was performed using common MR methods including inverse variance weighted (IVW), weighted median (WME), MR-Egger, simple mode (SM), and weighted mode (WM). The causal relationship between gut microbiota and frontotemporal dementia was ultimately analyzed through the inverse variance weighted method. Heterogeneity was assessed using Q-test, pleiotropy was examined using pleiotropy function, horizontal pleiotropy was detected by mrpresso, and directionality was verified by Steiger test. Results: Genetic variants related to frontotemporal dementia were screened as instrumental variables. A causal association was found between Veillonella and frontotemporal dementia (OR=0.134, 95%CI: 0.028~0.637, P<0.05), between Family_XIII_UCG_001 of Ruminococcaceae and frontotemporal dementia (OR=10.672, 95%CI: 2.001~56.921, P<0.05). Heterogeneity tests showed no significant heterogeneity for Veillonella and Family_XIII_UCG_001 in relation to frontotemporal dementia (P>0.05). Horizontal pleiotropy tests indicated no significant horizontal pleiotropy effects for Veillonella and Family_XIII_UCG_001 with frontotemporal dementia (P>0.05). Mrpresso detected no horizontal pleiotropy (P>0.05), and Steiger test confirmed the directionality of Veillonella and Family_XIII_UCG_001 with frontotemporal dementia（P＜0. 05）. Conclusion Ruminococcus is negatively causally related to frontotemporal dementia, while Family_XIII_UCG_001 of Ruminoclostridium is positively causally related to frontotemporal dementia |
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