Therapeutic targets for gastrointestinal diseases: proteome-wide Mendelian randomization and colocalization analyses.

IF 3.6 4区医学 Q1 MEDICINE, GENERAL & INTERNAL Postgraduate Medical Journal Pub Date : 2024-10-14 DOI:10.1093/postmj/qgae140

Daqin Zhan, Zhihao Yang, Pengcheng Li, Jun Pan

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Abstract

Purpose: This study was aimed to identify serum proteins linked with gastrointestinal diseases by proteome-wide Mendelian randomization analysis.

Methods: We determined the casual relationship between 732 kinds of circulating proteins and the 24 kinds of gastrointestinal diseases via Mendelian randomization analysis.

Results: Four circulating proteins (FCGR3B, IL-12B, MAPKAPK2, and IL-23R) were associated with the occurrence of ulcerative colitis (UC), and IL23R was also correlated with risk of Crohn's disease (CD). Genetically predicted levels of IL23R were strongly correlated with the risk of UC and CD based on the high supporting evidence of colocalization analysis. Five circulating proteins (NOV, EFEMP1, ADGRE2, LCT, and SEMA3G) were associated with the risk of diverticulosis disease. With high supporting evidence of colocalization, genetically predicted levels of NOV and SEMA3G were inversely correlated with the risk of diverticulosis disease. Five circulating proteins (FUT3, FUT5, CRHBP, SULT2A1, and QPCTL) were associated with the occurrence of cholelithiasis. With high supporting evidence of colocalization, genetically predicted levels of FUT3 and CRHBP were inversely correlated with the risk of cholelithiasis.

Conclusions: The proteome-wide Mendelian randomization investigation identified several circulating proteins associated with the risk of UC, CD, diverticular disease and cholelithiasis, which reinforced the understanding of molecular pathogenesis and design of therapeutic targets.

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胃肠道疾病的治疗目标：全蛋白质组孟德尔随机化和共定位分析。

目的：本研究旨在通过全蛋白质组孟德尔随机分析法确定与胃肠道疾病相关的血清蛋白：方法：通过孟德尔随机分析法确定 732 种循环蛋白与 24 种胃肠道疾病之间的偶然关系：结果：4种循环蛋白（FCGR3B、IL-12B、MAPKAPK2和IL-23R）与溃疡性结肠炎（UC）的发生有关，IL-23R还与克罗恩病（CD）的风险相关。基于共定位分析的高度支持证据，基因预测的 IL23R 水平与溃疡性结肠炎和克罗恩病的风险密切相关。五种循环蛋白（NOV、EFEMP1、ADGRE2、LCT 和 SEMA3G）与憩室病风险相关。NOV和SEMA3G的基因预测水平与憩室病的患病风险成反比，具有高度的共定位支持证据。五种循环蛋白（FUT3、FUT5、CRHBP、SULT2A1 和 QPCTL）与胆石症的发生有关。FUT3和CRHBP的基因预测水平与胆石症的风险成反比，具有高度的共定位支持证据：全蛋白质组孟德尔随机化调查发现了几种与UC、CD、憩室疾病和胆石症风险相关的循环蛋白质，这加深了人们对分子发病机制的理解，有助于设计治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Postgraduate Medical Journal 医学-医学：内科

CiteScore

8.50

自引率

2.00%

发文量

131

审稿时长

2.5 months

期刊介绍： Postgraduate Medical Journal is a peer reviewed journal published on behalf of the Fellowship of Postgraduate Medicine. The journal aims to support junior doctors and their teachers and contribute to the continuing professional development of all doctors by publishing papers on a wide range of topics relevant to the practicing clinician and teacher. Papers published in PMJ include those that focus on core competencies; that describe current practice and new developments in all branches of medicine; that describe relevance and impact of translational research on clinical practice; that provide background relevant to examinations; and papers on medical education and medical education research. PMJ supports CPD by providing the opportunity for doctors to publish many types of articles including original clinical research; reviews; quality improvement reports; editorials, and correspondence on clinical matters.