肠道菌群与肾细胞癌关系的孟德尔随机化分析

Mendelian randomization analysis of the relationship between gut microbiota and renal cell carcinoma

摘要

目的 采用孟德尔随机化分析探索肠道菌群组成与肾细胞癌（RCC）之间的因果关系。方法 检索MiBioGen联盟中参与肠道微生物组全基因组关联研究者的统计数据作为暴露组数据，RCC数据来自FinnGen全基因组关联研究（GWAS）数据库。采用的孟德尔随机化分析方法包括逆方差加权（IVW）、MR-Egger、最大似然和加权中位数。采用敏感性分析以解决异质性和水平多效性问题。结果 对来自完整肠道菌群的2564个单核苷酸多态性（SNPs）进行了分析。IVW分析显示芽孢杆菌纲（OR=0.780，95%CI：0.614～0.991，P=0.042）和厌氧菌属（OR=0.723，95%CI：0.533～0.981，P=0.037）与RCC降低存在因果关系。放线菌纲（OR=1.302，95%CI：1.015～1.672，P=0.038）、Family Ⅺ科（OR=1.197，95%CI：1.023～1.400，P=0.024）、粪球菌2属（OR=1.440，95%CI：1.046～1.982，P=0.026）、乳酸芽孢梭菌属（OR=1.732，95%CI：1.254～2.392，P=0.001）和Odoribacter属（OR=1.685，95%CI：1.150～2.469，P=0.007）则与RCC增加存在因果关系。敏感性分析没有发现任何异常的SNPs，表明本研究结果具有稳健性和可靠性。结论 肠道菌群与RCC之间可能存在正向因果关系，不同菌群分别与基因预测的RCC的增加或降低有关。

Abstract

Objective To explore the correlation between gut microbiota and renal cell carcinoma (RCC) with Mendelian randomization analysis. Methods Data involved with genome-wide association of the gut microbiome were retrieved from MiBioGen Consortium as the exposure group data, and RCC data were obtained from the FinnGen GWAS database. Next, a rigorous Mendelian randomization analysis was conducted utilizing multiple methods, including inverse variance weighted (IVW), MR-Egger, maximum likelihood, and weighted median. Additionally, sensitivity analysis was performed to address heterogeneity and horizontal pleiotropy concerns. Results A total of 2564 single nucleotide polymorphisms (SNPs) from the complete gut microbiota were analyzed. IVW analysis showed that bacillus (OR=0.780, 95%CI: 0.614-0.991, P=0.042) and anaerobic bacillus (OR=0.723, 95%CI: 0.533-0.981, P=0.037) reduced the risk of RCC. Actinomycetes (OR=1.302, 95%CI: 1.015-1.672, P=0.038), family Ⅺ (OR=1.197, 95%CI: 1.023-1.400, P=0.024), coprococcus 2 genera (OR=1.440, 95%CI: 1.046-1.982, P=0.026), clostridium lactate (OR=1.732, 95%CI: 1.254-2.392, P=0.001) and Odoribacter (OR=1.685, 95%CI: 1.150-2.469, P=0.007) were associated with an increased risk of RCC. Sensitivity analysis did not identify any abnormal SNPs, indicating the robustness and reliability of our findings. Conclusion There may be a cause-and-effect relationship between different types of gut microbiota and genetically predicted renal cell carcinoma, and different microbiota may be respectively associated with an increase or decrease in RCC.

关键词

肾细胞癌 / 肠道菌群 / 逆方差加权 / 单核苷酸多态性 / 孟德尔随机化

Key words

renal cell carcinoma / gut microbiota / inverse variance weighted / single nucleotide polymorphism / Mendelian randomization

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