GNLY 是抑制前列腺炎的顺式-eQTL 和顺式-pQTL 介导的新型易感基因。孟德尔随机化研究。

IF 4.7 3区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Archives of Medical Research Pub Date : 2024-10-21 DOI:10.1016/j.arcmed.2024.103098

Yi Wang , Hao Ji , Guihua Chen , Jianhua Zhou , Dongliang Zhang , Xiang Wang

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引用次数: 0

摘要

背景：前列腺炎具有发病率高、治愈率低和复发频繁的特点，仍然是临床上最具挑战性的问题之一。因此，在本文中，我们首次将孟德尔随机化（MR）与表达定量性状位点（eQTL）和蛋白质定量性状位点（pQTL）数据整合在一起，以确定前列腺炎的新型治疗靶点及其潜在的代谢机制：方法：从在线数据库中下载与前列腺炎相关的遗传数据、eQTL、pQTL 和 1400 种代谢物。应用MR或基于数据摘要的MR（SMR）分析评估暴露与预测结果之间的潜在因果关系。为了评估结果的稳健性，我们采用了多向性分析、异质性分析和排除分析等方法进行了敏感性分析：基于我们的研究结果，我们首先在五个独立数据集（一个发现数据集和四个验证数据集）中发现并验证了GNLY是一个新型顺式-eQTL和顺式-pQTL介导的降低前列腺炎风险的易感基因（均为p 结论：我们成功地发现了GNLY是一个新型顺式-eQTL和顺式-pQTL介导的降低前列腺炎风险的易感基因：我们成功地发现了GNLY是一种新型的顺式-eQTL和顺式-pQTL介导的易感基因，它通过调节鞘磷脂（d18:0/20:0, d16:0/22:0）水平来抑制前列腺炎及其潜在的代谢机制，从而提供了一种新型的治疗靶点，并为今后GNLY在前列腺炎中的相关研究铺平了道路。

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GNLY as a novel cis-eQTL and cis-pQTL mediated susceptibility gene in suppressing prostatitis. Mendelian randomization study

Background

Prostatitis is characterized by high prevalence, low cure rates, and frequent recurrences, and remains one of the most clinically challenging problems. Hence, in this article, we first integrated Mendelian randomization (MR) with expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL) data to identify novel therapeutic targets and their potential metabolic mechanisms for prostatitis.

Methods

Prostatitis-related genetic data, eQTLs, pQTLs, and 1400 metabolites were downloaded from online databases. MR, or summary data-based MR (SMR) analyses were applied to assess the potential causal relationships between exposures and predicted outcomes. Sensitivity analysis was conducted using pleiotropy, heterogeneity, and leave-one-out analysis to evaluate the robustness of our results.

Results

Based on our results, we first identified and validated GNLY as a novel cis-eQTL and cis-pQTL-mediated susceptibility gene for reducing prostatitis risk in five independent datasets (one discovery dataset and four validation datasets) (all p <0.05). Meanwhile, we also found that the GNLY eQTL could increase the metabolite of sphingomyelin level (d18:0/20:0, d16:0/22:0) risks (p <0.05), and the metabolite of sphingomyelin level (d18:0/20:0, d16:0/22:0) could reduce the risk of prostatitis (p <0.05). According to the above-mentioned relationships, we finally revealed the potential metabolic mechanism of GNLY eQTL in suppressing prostatitis via regulating the metabolite of sphingomyelin level (d18:0/20:0, d16:0/22:0).

Conclusions

We successfully identified GNLY as a novel cis-eQTL and cis-pQTL-mediated susceptibility gene in suppressing prostatitis and its potential metabolic mechanism via regulating sphingomyelin (d18:0/20:0, d16:0/22:0) levels, providing a novel therapeutic target and paving the way for future GNLY-related studies in prostatitis.

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来源期刊

Archives of Medical Research 医学-医学：研究与实验

CiteScore

12.50

自引率

0.00%

发文量

审稿时长

28 days

期刊介绍： Archives of Medical Research serves as a platform for publishing original peer-reviewed medical research, aiming to bridge gaps created by medical specialization. The journal covers three main categories - biomedical, clinical, and epidemiological contributions, along with review articles and preliminary communications. With an international scope, it presents the study of diseases from diverse perspectives, offering the medical community original investigations ranging from molecular biology to clinical epidemiology in a single publication.