{"title":"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。","authors":"Daqin Zhan, Zhihao Yang, Pengcheng Li, Jun Pan","doi":"10.1093/postmj/qgae140","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>This study was aimed to identify serum proteins linked with gastrointestinal diseases by proteome-wide Mendelian randomization analysis.</p><p><strong>Methods: </strong>We determined the casual relationship between 732 kinds of circulating proteins and the 24 kinds of gastrointestinal diseases via Mendelian randomization analysis.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":20374,"journal":{"name":"Postgraduate Medical Journal","volume":" ","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Therapeutic targets for gastrointestinal diseases: proteome-wide Mendelian randomization and colocalization analyses.\",\"authors\":\"Daqin Zhan, Zhihao Yang, Pengcheng Li, Jun Pan\",\"doi\":\"10.1093/postmj/qgae140\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>This study was aimed to identify serum proteins linked with gastrointestinal diseases by proteome-wide Mendelian randomization analysis.</p><p><strong>Methods: </strong>We determined the casual relationship between 732 kinds of circulating proteins and the 24 kinds of gastrointestinal diseases via Mendelian randomization analysis.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>\",\"PeriodicalId\":20374,\"journal\":{\"name\":\"Postgraduate Medical Journal\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2024-10-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Postgraduate Medical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1093/postmj/qgae140\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Postgraduate Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/postmj/qgae140","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Therapeutic targets for gastrointestinal diseases: proteome-wide Mendelian randomization and colocalization analyses.
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.
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.
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