Yi Wang , Hao Ji , Guihua Chen , Jianhua Zhou , Dongliang Zhang , Xiang Wang
{"title":"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。","authors":"Yi Wang , Hao Ji , Guihua Chen , Jianhua Zhou , Dongliang Zhang , Xiang Wang","doi":"10.1016/j.arcmed.2024.103098","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>p</em> <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 (<em>p</em> <0.05), and the metabolite of sphingomyelin level (d18:0/20:0, d16:0/22:0) could reduce the risk of prostatitis (<em>p</em> <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).</div></div><div><h3>Conclusions</h3><div>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.</div></div>","PeriodicalId":8318,"journal":{"name":"Archives of Medical Research","volume":null,"pages":null},"PeriodicalIF":4.7000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"GNLY as a novel cis-eQTL and cis-pQTL mediated susceptibility gene in suppressing prostatitis. 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Sensitivity analysis was conducted using pleiotropy, heterogeneity, and leave-one-out analysis to evaluate the robustness of our results.</div></div><div><h3>Results</h3><div>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 <em>p</em> <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 (<em>p</em> <0.05), and the metabolite of sphingomyelin level (d18:0/20:0, d16:0/22:0) could reduce the risk of prostatitis (<em>p</em> <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).</div></div><div><h3>Conclusions</h3><div>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.</div></div>\",\"PeriodicalId\":8318,\"journal\":{\"name\":\"Archives of Medical Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-10-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Medical Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0188440924001498\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Medical Research","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0188440924001498","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
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.
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.