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探索因果关系:良性前列腺增生与心血管疾病的双向孟德尔随机化研究

Exploring the causal relationship: bidirectional mendelian randomization study on benign prostatic hyperplasia and cardiovascular diseases.

作者信息

Xiang Nanyan, Su Shiqi, Wang Zeng, Yang Yong, Chen Boxi, Shi Rui, Zheng Tao, Liao Banghua, Lin Yifei, Huang Jin

机构信息

Department of Urology, Innovation Institute for Integration of Medicine and Engineering, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Chengdu, Sichuan, China.

Engineering Research Center of Medical Information Technology, Ministry of Education, West China Hospital of Sichuan University, Chengdu, Sichuan, China.

出版信息

Front Genet. 2024 Jul 26;15:1432055. doi: 10.3389/fgene.2024.1432055. eCollection 2024.

Abstract

BACKGROUND

Benign prostatic hyperplasia (BPH) is a common disease occurring in elderly and middle-aged men, and cardiovascular diseases (CVDs) are one of the major causes of death worldwide. Many observational studies examined have found a strong association between BPH and CVDs, but the causal relationship between them is unclear. The aim of this study was to determine the causal relationship between BPH and CVDs, specifically five diseases: stroke, coronary heart disease (CHD), heart failure, myocardial infarction (MI), and atrial fibrillation (AF).

METHODS

In this study, we obtained single nucleotide polymorphisms (SNPs) of patients with BPH from the UK Biobank database and patients with CVDs from the UK Biobank, the HERMES Consortium, and the FinnGen Genome Database, each used as a genetic tool for a Mendelian randomization (MR) study. We used conventional MR analysis to assess potential causal direction between BPH and CVDs, as well as MR-Egger, MR-PRESSO, model-based estimation (MBE) and weighted median methods for sensitivity analysis.

RESULTS

Using a bidirectional two-sample MR study, we found that BPH patients had an increased risk of developing CHD (ConMix OR = 1.152, 95% CI: 1.011-1.235, = 0.035) and MI (ConMix OR = 1.107.95% CI: 1.022-1.164, = 0.013), but a decreased risk of stroke (ConMix OR = 0.872, 95% CI: 0.797-0.926, = 0.002). The reverse study was not statistically significant and further research may be needed.

CONCLUSION

Our study suggests a potential causal relationship between BPH and CVDs. BPH appears to be a risk factor for CHD and MI, but it may be protective against stroke. There was no evidence of a causal association in the reverse study, and a larger sample size was needed in follow-up to further explore the potential association.

摘要

背景

良性前列腺增生(BPH)是中老年男性的常见疾病,而心血管疾病(CVD)是全球主要死因之一。许多已开展的观察性研究发现BPH与CVD之间存在密切关联,但它们之间的因果关系尚不清楚。本研究的目的是确定BPH与CVD之间的因果关系,特别是五种疾病:中风、冠心病(CHD)、心力衰竭、心肌梗死(MI)和心房颤动(AF)。

方法

在本研究中,我们从英国生物银行数据库获取了BPH患者的单核苷酸多态性(SNP),并从英国生物银行、HERMES联盟和芬兰基因组数据库获取了CVD患者的SNP,每个数据库都用作孟德尔随机化(MR)研究的遗传工具。我们使用传统的MR分析来评估BPH与CVD之间的潜在因果方向,以及用于敏感性分析的MR-Egger、MR-PRESSO、基于模型的估计(MBE)和加权中位数方法。

结果

通过双向双样本MR研究,我们发现BPH患者患CHD(ConMix OR = 1.152,95% CI:1.011 - 1.235,P = 0.035)和MI(ConMix OR = 1.107,95% CI:1.022 - 1.164,P = 0.013)的风险增加,但中风风险降低(ConMix OR = 0.872,95% CI:0.797 - 0.926,P = 0.002)。反向研究无统计学意义且可能需要进一步研究。

结论

我们的研究表明BPH与CVD之间存在潜在因果关系。BPH似乎是CHD和MI的危险因素,但可能对中风有保护作用。反向研究中没有因果关联的证据,后续需要更大样本量以进一步探索潜在关联。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a87f/11310031/d989e9e462d8/fgene-15-1432055-g001.jpg

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