Suppr超能文献

探索血清代谢物与勃起功能障碍之间的因果关联:一项双向孟德尔随机化研究。

Exploring the causal association between serum metabolites and erectile dysfunction: a bidirectional Mendelian randomisation study.

作者信息

Xu Ran, Liu Shuo, Li Lu-Yi, Bu Yue, Bai Pei-Ming, Luo Guang-Cheng, Wang Xin-Jun

机构信息

Department of Urology, Zhongshan Hospital Xiamen University, School of Medicine, Xiamen University, Xiamen, China.

Department of Urology, Zhongshan Hospital Xiamen University, The School of Clinical Medicine, Fujian Medical University, Xiamen, China.

出版信息

Int J Impot Res. 2024 Jun 10. doi: 10.1038/s41443-024-00926-2.

Abstract

Erectile dysfunction is a common sexual disorder in men. Some studies have found a strong association between some serum metabolites and erectile dysfunction. To investigate this association further, we used bidirectional Mendelian randomisation to investigate causality and possible biological mechanisms.Firstly, this study screened the statistics of genome-wide association studies of serum metabolites and erectile dysfunction to obtain instrumental variables. Inverse variance weighting was used as the primary method for causal effect analysis of instrumental variables in forward or reverse Mendelian randomisation, and the results obtained by MR-Egger regression and the weighted median method were used as references. Subsequently, the metabolites causally associated with erectile dysfunction were subjected to replication analyses and meta-analyses, and the results of the meta-analyses were analysed by pathway analyses to find influential pathways. In this process, Mendelian randomisation results need to be assessed for stability and reliability using sensitivity analysis.It was found that a total of six serum metabolites were causally associated with erectile dysfunction in a forward Mendelian randomisation study. 1,3,7-trimethyluraten (0.85 (0.73-0.99), P = 0.0368), ergothioneine (0.65 (0.45-0.94), P = 0.0226) and gamma-glutamylglutamate (0.63 (0.46-0.88), P = 0.0059) were protective against the development of erectile dysfunction, whereas 2-hydroxyhippurate (1.10 (1.02-1.19), P = 0.0152), N2,N2-dimethylguanosine (1.57 (1.02-2.40), P = 0.0395) and octanoylcarnitine (1.38 (1.06-1.82), P = 0.0183) were able to induce the development of erectile dysfunction. In addition, metabolic pathway analysis showed that 1,3,7-trimethylurate was able to influence the development of erectile dysfunction via the caffeine metabolism pathway (P = 0.0454). On the other hand, reverse Mendelian randomisation analysis showed that erectile dysfunction reduced serum homocitrulline levels (0.99 (0.97-1.00), P = 0.0360). Sensitivity analyses, including heterogeneity tests and pleiotropy tests, confirmed the reliability of the results.In conclusion, this study demonstrated a bidirectional causal relationship between serum metabolites and erectile dysfunction using bidirectional Mendelian randomisation analysis and replication meta-analysis. On this basis, this study provides a new direction of thinking and strong evidence for the therapeutic application and adjunctive diagnosis of serum metabolites in erectile dysfunction, and provides a certain reference value for subsequent related studies.

摘要

勃起功能障碍是男性常见的性功能障碍。一些研究发现某些血清代谢物与勃起功能障碍之间存在密切关联。为了进一步研究这种关联,我们采用双向孟德尔随机化来研究因果关系和可能的生物学机制。首先,本研究筛选了血清代谢物和勃起功能障碍的全基因组关联研究统计数据以获得工具变量。逆方差加权被用作正向或反向孟德尔随机化中工具变量因果效应分析的主要方法,MR-Egger回归和加权中位数法得到的结果用作参考。随后,对与勃起功能障碍有因果关联的代谢物进行重复分析和荟萃分析,并通过通路分析对荟萃分析结果进行分析以找到有影响的通路。在此过程中,需要使用敏感性分析评估孟德尔随机化结果的稳定性和可靠性。发现在一项正向孟德尔随机化研究中,共有六种血清代谢物与勃起功能障碍存在因果关联。1,3,7-三甲基尿酸盐(0.85(0.73 - 0.99),P = 0.0368)、麦角硫因(0.65(0.45 - 0.94),P = 0.0226)和γ-谷氨酰谷氨酸(0.63(0.46 - 0.88),P = 0.0059)对勃起功能障碍的发生有保护作用,而2-羟基马尿酸(1.10(1.02 - 1.19),P = 0.0152)、N2,N2-二甲基鸟苷(1.57(1.02 - 2.40),P = 0.0395)和辛酰肉碱(1.38(1.06 - 1.82),P = 0.0183)能够诱导勃起功能障碍的发生。此外,代谢通路分析表明1,3,7-三甲基尿酸盐能够通过咖啡因代谢通路影响勃起功能障碍的发生(P = 0.0454)。另一方面,反向孟德尔随机化分析表明勃起功能障碍会降低血清高瓜氨酸水平(0.99(0.97 - 1.00),P = 0.0360)。包括异质性检验和多效性检验在内的敏感性分析证实了结果的可靠性。总之,本研究使用双向孟德尔随机化分析和重复荟萃分析证明了血清代谢物与勃起功能障碍之间的双向因果关系。在此基础上,本研究为血清代谢物在勃起功能障碍的治疗应用和辅助诊断提供了新方向和有力证据,并为后续相关研究提供了一定参考价值。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验