遗传和血浆蛋白质组学方法确定Graves病和Graves眼病的治疗靶点。

IF 6.2 Q1 IMMUNOLOGY
ImmunoTargets and Therapy Pub Date : 2025-02-07 eCollection Date: 2025-01-01 DOI:10.2147/ITT.S494692
Chenxin Ke, Yuefeng Yu, Jiang Li, Yuetian Yu, Ying Sun, Yuying Wang, Bin Wang, Yingli Lu, Mengjun Tang, Ningjian Wang, Yi Chen
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引用次数: 0

摘要

背景:血液蛋白质组是生物标志物和治疗靶点的主要来源。我们旨在通过系统的遗传分析确定Graves病(GD)和Graves眼病(GO)的致病蛋白和潜在靶点。方法:UK Biobank- Pharma Proteomics Project (UKB-PPP)的全基因组关联研究(GWASs)从54,219名参与者中收集了2923个Olink蛋白。我们使用顺式pqtl进行了一项全蛋白质组孟德尔随机化(MR)研究,以确定GD和GO风险的候选蛋白。使用共定位分析和Heidi测试来检查鉴定的蛋白质和疾病是否具有相同的变体。在使用反式pqtl的基于汇总数据的MR (SMR)分析中,发现了更多具有潜在因果关联的蛋白质。然后,进行下游分析以检测蛋白质相互作用、基因功能、细胞类型特异性表达和药物信息。结果:本研究预测了与GD风险相关的62种血浆蛋白水平。四种蛋白(CD40, TINAGL1, GMPR和CXCL10)被优先考虑与GD共享相同变体的证据。具体来说,一些蛋白质与GD有潜在的关联,在CD40中有反式pqtl定位。这4个优先蛋白编码基因主要富集于细胞凋亡和死亡过程的调控。此外,GMPR与GO和GD均呈一致方向相关。BTN1A1和FCRL1被优先考虑为GO发病的致病蛋白,与GD无关。结论:通过合成蛋白质组学和遗传学数据,我们确定了GD的几个蛋白质生物标志物,其中一个与GD和GO相关,另外两个与GO发病相关的蛋白质生物标志物,为这两种疾病的病因学和潜在治疗靶点提供了有价值的见解。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic and Plasma Proteomic Approaches to Identify Therapeutic Targets for Graves' Disease and Graves' Ophthalmopathy.

Background: The blood proteome is a major source of biomarkers and therapeutic targets. We aimed to identify the causal proteins and potential targets for Graves' disease (GD) and Graves' ophthalmopathy (GO) via systematic genetic analyses.

Methods: Genome-wide association studies (GWASs) on the UK Biobank- Pharma Proteomics Project (UKB-PPP) collected 2923 Olink proteins from 54,219 participants. We conducted a proteome-wide Mendelian randomization (MR) study with cis-pQTLs to identify candidate proteins for GD and GO risk. Colocalization analysis and the Heidi test were used to examine whether the identified proteins and diseases shared the same variant. More proteins with potential causal associations were identified in Summary-data-based MR (SMR) analyses using trans-pQTLs. Then, downstream analyses were performed to detect protein interactions, gene function, cell type-specific expression and druggable information.

Results: This study genetically predicted levels of 62 plasma proteins were associated with GD risk. Four proteins (CD40, TINAGL1, GMPR and CXCL10) were prioritized with the evidence of sharing the same variants with GD. Specifically, some proteins had potential associations with GD with trans-pQTLs mapping in CD40. The four prioritized protein-coding genes were mainly enriched in the regulation of apoptotic and death processes. In addition, GMPR was associated with both GO and GD in a consistent direction. BTN1A1 and FCRL1 were prioritized as the causal proteins for GO onset and were not associated with GD.

Conclusion: By synthesizing proteomic and genetic data, we identified several protein biomarkers for GD, with one linked to both GD and GO and two other protein biomarkers specific to GO onset, which provides valuable insights into the etiology and potential therapeutic targets for the two diseases.

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来源期刊
CiteScore
16.50
自引率
0.00%
发文量
7
审稿时长
16 weeks
期刊介绍: Immuno Targets and Therapy is an international, peer-reviewed open access journal focusing on the immunological basis of diseases, potential targets for immune based therapy and treatment protocols employed to improve patient management. Basic immunology and physiology of the immune system in health, and disease will be also covered.In addition, the journal will focus on the impact of management programs and new therapeutic agents and protocols on patient perspectives such as quality of life, adherence and satisfaction.
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