利用孟德尔随机分析鉴定治疗炎症性肠病的潜在新靶点。

IF 2.5 3区 医学 Q2 GASTROENTEROLOGY & HEPATOLOGY
Ji-Chang Fan, Yuan Lu, Jin-Heng Gan, Hao Lu
{"title":"利用孟德尔随机分析鉴定治疗炎症性肠病的潜在新靶点。","authors":"Ji-Chang Fan, Yuan Lu, Jin-Heng Gan, Hao Lu","doi":"10.1007/s00384-024-04744-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a complex autoimmune disorder, although some medications are available for its treatment. However, the long-term efficacy of these drugs remains unsatisfactory. Therefore, there is a need to develop novel drug targets for IBD treatment.</p><p><strong>Methods: </strong>We conducted two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) data to assess the causal relationships between plasma proteins and IBD and its subtypes. Subsequently, the presence of shared genetic variants between the identified plasma proteins and traits was explored using Bayesian co-localization. Phenome-wide MR was used to evaluate evaluated adverse effects, and drug target databases were examined for therapeutic potential.</p><p><strong>Results: </strong>Using the Bonferroni correction (P < 3.56e-05), 17 protein-IBD pairs were identified. Notably, the genetic associations of IBD shared a common variant locus (PP.H4 > 0.7) with five proteins (MST1, IL12B, HGFAC, FCGR2A, and IL18R1). As a subtype of IBD, ulcerative colitis shares common variant loci with FCGR2A, IL12B, and MST1. In addition, we found that ANGPTL3, IL18R1, and MST1 share a common variant locus with Crohn's disease. Furthermore, phenome-wide MR analysis revealed that except for ANGPTL3, no other proteins showed potential adverse effects. In the drug database, identified plasma proteins such as FCGR2A and IL18R1 were found to be potential drug targets for the treatment of IBD and its subtypes.</p><p><strong>Conclusion: </strong>Six proteins (FCGR2A, IL18R1, MST1, HGFAC, IL12B, and ANGPTL3) were identified as potential drug targets for the treatment of IBD and its subtypes.</p>","PeriodicalId":13789,"journal":{"name":"International Journal of Colorectal Disease","volume":"39 1","pages":"165"},"PeriodicalIF":2.5000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485038/pdf/","citationCount":"0","resultStr":"{\"title\":\"Identification of potential novel targets for treating inflammatory bowel disease using Mendelian randomization analysis.\",\"authors\":\"Ji-Chang Fan, Yuan Lu, Jin-Heng Gan, Hao Lu\",\"doi\":\"10.1007/s00384-024-04744-2\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Inflammatory bowel disease (IBD) is a complex autoimmune disorder, although some medications are available for its treatment. However, the long-term efficacy of these drugs remains unsatisfactory. Therefore, there is a need to develop novel drug targets for IBD treatment.</p><p><strong>Methods: </strong>We conducted two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) data to assess the causal relationships between plasma proteins and IBD and its subtypes. Subsequently, the presence of shared genetic variants between the identified plasma proteins and traits was explored using Bayesian co-localization. Phenome-wide MR was used to evaluate evaluated adverse effects, and drug target databases were examined for therapeutic potential.</p><p><strong>Results: </strong>Using the Bonferroni correction (P < 3.56e-05), 17 protein-IBD pairs were identified. Notably, the genetic associations of IBD shared a common variant locus (PP.H4 > 0.7) with five proteins (MST1, IL12B, HGFAC, FCGR2A, and IL18R1). As a subtype of IBD, ulcerative colitis shares common variant loci with FCGR2A, IL12B, and MST1. In addition, we found that ANGPTL3, IL18R1, and MST1 share a common variant locus with Crohn's disease. Furthermore, phenome-wide MR analysis revealed that except for ANGPTL3, no other proteins showed potential adverse effects. In the drug database, identified plasma proteins such as FCGR2A and IL18R1 were found to be potential drug targets for the treatment of IBD and its subtypes.</p><p><strong>Conclusion: </strong>Six proteins (FCGR2A, IL18R1, MST1, HGFAC, IL12B, and ANGPTL3) were identified as potential drug targets for the treatment of IBD and its subtypes.</p>\",\"PeriodicalId\":13789,\"journal\":{\"name\":\"International Journal of Colorectal Disease\",\"volume\":\"39 1\",\"pages\":\"165\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-10-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11485038/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Colorectal Disease\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00384-024-04744-2\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"GASTROENTEROLOGY & HEPATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Colorectal Disease","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00384-024-04744-2","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"GASTROENTEROLOGY & HEPATOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:炎症性肠病(IBD)是一种复杂的自身免疫性疾病:炎症性肠病(IBD)是一种复杂的自身免疫性疾病,虽然目前已有一些药物可用于治疗。然而,这些药物的长期疗效仍不令人满意。因此,有必要开发治疗 IBD 的新型药物靶点:方法:我们利用全基因组关联研究(GWAS)数据进行了双样本孟德尔随机化(MR)分析,以评估血浆蛋白与 IBD 及其亚型之间的因果关系。随后,利用贝叶斯共定位法探讨了已确定的血浆蛋白与性状之间是否存在共享遗传变异。全表型MR用于评估所评价的不良反应,药物靶点数据库则用于研究治疗潜力:通过对五种蛋白质(MST1、IL12B、HGFAC、FCGR2A 和 IL18R1)进行 Bonferroni 校正(P0.7),结果表明作为 IBD 的一种亚型,溃疡性结肠炎与 FCGR2A、IL12B 和 MST1 有共同的变异位点。此外,我们还发现 ANGPTL3、IL18R1 和 MST1 与克罗恩病有共同的变异位点。此外,全表型 MR 分析表明,除 ANGPTL3 外,其他蛋白均未显示出潜在的不良反应。在药物数据库中,发现FCGR2A和IL18R1等血浆蛋白是治疗IBD及其亚型的潜在药物靶点:结论:六种蛋白质(FCGR2A、IL18R1、MST1、HGFAC、IL12B和ANGPTL3)被确定为治疗IBD及其亚型的潜在药物靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Identification of potential novel targets for treating inflammatory bowel disease using Mendelian randomization analysis.

Background: Inflammatory bowel disease (IBD) is a complex autoimmune disorder, although some medications are available for its treatment. However, the long-term efficacy of these drugs remains unsatisfactory. Therefore, there is a need to develop novel drug targets for IBD treatment.

Methods: We conducted two-sample Mendelian randomization (MR) analysis using Genome-Wide Association Study (GWAS) data to assess the causal relationships between plasma proteins and IBD and its subtypes. Subsequently, the presence of shared genetic variants between the identified plasma proteins and traits was explored using Bayesian co-localization. Phenome-wide MR was used to evaluate evaluated adverse effects, and drug target databases were examined for therapeutic potential.

Results: Using the Bonferroni correction (P < 3.56e-05), 17 protein-IBD pairs were identified. Notably, the genetic associations of IBD shared a common variant locus (PP.H4 > 0.7) with five proteins (MST1, IL12B, HGFAC, FCGR2A, and IL18R1). As a subtype of IBD, ulcerative colitis shares common variant loci with FCGR2A, IL12B, and MST1. In addition, we found that ANGPTL3, IL18R1, and MST1 share a common variant locus with Crohn's disease. Furthermore, phenome-wide MR analysis revealed that except for ANGPTL3, no other proteins showed potential adverse effects. In the drug database, identified plasma proteins such as FCGR2A and IL18R1 were found to be potential drug targets for the treatment of IBD and its subtypes.

Conclusion: Six proteins (FCGR2A, IL18R1, MST1, HGFAC, IL12B, and ANGPTL3) were identified as potential drug targets for the treatment of IBD and its subtypes.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
4.90
自引率
3.60%
发文量
206
审稿时长
3-8 weeks
期刊介绍: The International Journal of Colorectal Disease, Clinical and Molecular Gastroenterology and Surgery aims to publish novel and state-of-the-art papers which deal with the physiology and pathophysiology of diseases involving the entire gastrointestinal tract. In addition to original research articles, the following categories will be included: reviews (usually commissioned but may also be submitted), case reports, letters to the editor, and protocols on clinical studies. The journal offers its readers an interdisciplinary forum for clinical science and molecular research related to gastrointestinal disease.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信