关键词: Mendelian randomization SNPs cardiac tumor gut microbiota

Mesh : Humans Mendelian Randomization Analysis Gastrointestinal Microbiome / genetics Genome-Wide Association Study Genetic Predisposition to Disease Polymorphism, Single Nucleotide Heart Neoplasms / genetics microbiology Risk Factors

来  源:   DOI:10.1002/cam4.7455   PDF(Pubmed)

Abstract:
BACKGROUND: Recent studies provide compelling evidence linking the gut microbiota to most cancers. Nevertheless, further research is required to establish a definitive causal relationship between the gut microbiota and malignant cardiac tumors.
METHODS: The genome-wide association studies (GWAS) data on the human gut Microbiota, included in the IEU Open GWAS project, was initially collected by the MiBioGen consortium. It encompasses 14,306 individuals and comprises a total of 5,665,279 SNPs. Similarly, the GWAS data on malignant cardiac tumors, also sourced from the IEU Open GWAS project, was initially stored in the finnGen database, including 16,380,303 SNPs observed within a cohort of 174,108 individuals within the European population. Utilizing a two-sample Mendelian randomization (MR) methodology, we examined whether there exists a causal association between the gut microbiota and cardiac tumors. Additionally, to bolster the credibility and robustness of the identified causal relationships, we conducted an extensive array of sensitivity analyses, encompassing Cochran\'s Q test, MR-PRESSO tests, MR-Egger interpret test, directionality test and leave-one-out analysis.
RESULTS: Our analysis unveiled seven distinct causal associations between genetic susceptibility in the gut microbiota and the incidence of malignant cardiac tumors. Among these, the Family Rikenellaceae, genus Eubacterium brachy group, and genus Ruminococcaceae UCG009 exhibited an elevated risk of cardiac tumors, while the phylum Verrucomicrobia, genus Lactobacillus, genus Ruminiclostridium5, and an unknown genus id.1868 were genetically linked to a reduced risk of cardiac tumors. The causal relationship between these two bacteria, belonging to the phylum Verrucomicrobia (OR = 0.178, 95% CI: 0.052-0.614, p = 0.006) and the genus Ruminococcaceae UCG009 (OR = 3.071, 95% CI: 1.236-7.627, p = 0.016), and cardiac tumors was further validated through sensitivity analyses, reinforcing the robustness and reliability of the observed associations.
CONCLUSIONS: Our MR analysis confirms that the phylum Verrucomicrobia displays significant protection against cardiac tumor, and the genus Ruminococcaceae UCG009 leads to an increasing risk of cardiac tumor.
摘要:
背景:最近的研究提供了令人信服的证据将肠道微生物群与大多数癌症联系起来。然而,需要进一步的研究来确定肠道微生物群与恶性心脏肿瘤之间的因果关系。
方法:关于人类肠道微生物群的全基因组关联研究(GWAS)数据,包括在IEUOpenGWAS项目中,最初是由MiBioGen财团收集的。它包括14,306个个体并且包含总共5,665,279个SNP。同样,关于恶性心脏肿瘤的GWAS数据,也来自IEUOpenGWAS项目,最初存储在finnGen数据库中,包括在欧洲人群中174,108个人的队列中观察到的16,380,303个SNP。利用双样本孟德尔随机化(MR)方法,我们研究了肠道菌群与心脏肿瘤之间是否存在因果关系.此外,为了增强已识别的因果关系的可信度和稳健性,我们进行了广泛的敏感性分析,包括科克伦的Q测试,MR-PRESSO测试,MR-Egger解释测试,方向性测试和留一法分析。
结果:我们的分析揭示了肠道微生物群遗传易感性与恶性心脏肿瘤发病率之间的七个不同的因果关系。其中,Rikenellaceae家族,肠杆菌属,短杆菌属,和Ruminocycaceae属UCG009表现出心脏肿瘤的风险升高,而微生物门,乳杆菌属,Ruminiclostridium5属和一个未知属id.1868在遗传上与降低心脏肿瘤的风险有关。这两种细菌之间的因果关系,属于棘藻门(OR=0.178,95%CI:0.052-0.614,p=0.006)和RuminococycaceaeUCG009(OR=3.071,95%CI:1.236-7.627,p=0.016),心脏肿瘤通过敏感性分析进一步验证,加强观察到的关联的稳健性和可靠性。
结论:我们的MR分析证实,棘藻门对心脏肿瘤具有显著的保护作用,和Ruminocycaceae属UCG009导致心脏肿瘤的风险增加。
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