{"title":"Innovate therapeutic targets for autoimmune diseases: insights from proteome-wide mendelian randomization and Bayesian colocalization.","authors":"Qiubai Jin, Feihong Ren, Ping Song","doi":"10.1080/08916934.2024.2330392","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Despite growing knowledge regarding the pathogenesis of autoimmune diseases (ADs) onset, the current treatment remains unsatisfactory. This study aimed to identify innovative therapeutic targets for ADs through various analytical approaches.</p><p><strong>Research design and methods: </strong>Utilizing Mendelian randomization, Bayesian co-localization, phenotype scanning, and protein-protein interaction network, we explored potential therapeutic targets for 14 ADs and externally validated our preliminary findings.</p><p><strong>Results: </strong>This study identified 12 circulating proteins as potential therapeutic targets for six ADs. Specifically, IL12B was judged to be a risk factor for ankylosing spondylitis (<i>p</i> = 1.61E - 07). TYMP (<i>p</i> = 6.28E - 06) was identified as a protective factor for ulcerative colitis. For Crohn's disease, ERAP2 (<i>p</i> = 4.47E - 14), HP (<i>p</i> = 2.08E - 05), and RSPO3 (<i>p</i> = 6.52E - 07), were identified as facilitators, whereas FLRT3 (<i>p</i> = 3.42E - 07) had a protective effect. In rheumatoid arthritis, SWAP70 (<i>p</i> = 3.26E - 10), SIGLEC6 (<i>p</i> = 2.47E - 05), ISG15 (<i>p</i> = 3.69E - 05), and FCRL3 (<i>p</i> = 1.10E - 10) were identified as risk factors. B4GALT1 (<i>p</i> = 6.59E - 05) was associated with a lower risk of Type 1 diabetes (T1D). Interestingly, CTSH was identified as a protective factor for narcolepsy (<i>p</i> = 1.58E - 09) but a risk factor for T1D (<i>p</i> = 7.36E - 11), respectively. External validation supported the associations of eight of these proteins with three ADs.</p><p><strong>Conclusions: </strong>Our integrated study identified 12 potential therapeutic targets for ADs and provided novel insights into future drug development for ADs.</p>","PeriodicalId":8688,"journal":{"name":"Autoimmunity","volume":null,"pages":null},"PeriodicalIF":3.3000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Autoimmunity","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/08916934.2024.2330392","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/3/22 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Despite growing knowledge regarding the pathogenesis of autoimmune diseases (ADs) onset, the current treatment remains unsatisfactory. This study aimed to identify innovative therapeutic targets for ADs through various analytical approaches.
Research design and methods: Utilizing Mendelian randomization, Bayesian co-localization, phenotype scanning, and protein-protein interaction network, we explored potential therapeutic targets for 14 ADs and externally validated our preliminary findings.
Results: This study identified 12 circulating proteins as potential therapeutic targets for six ADs. Specifically, IL12B was judged to be a risk factor for ankylosing spondylitis (p = 1.61E - 07). TYMP (p = 6.28E - 06) was identified as a protective factor for ulcerative colitis. For Crohn's disease, ERAP2 (p = 4.47E - 14), HP (p = 2.08E - 05), and RSPO3 (p = 6.52E - 07), were identified as facilitators, whereas FLRT3 (p = 3.42E - 07) had a protective effect. In rheumatoid arthritis, SWAP70 (p = 3.26E - 10), SIGLEC6 (p = 2.47E - 05), ISG15 (p = 3.69E - 05), and FCRL3 (p = 1.10E - 10) were identified as risk factors. B4GALT1 (p = 6.59E - 05) was associated with a lower risk of Type 1 diabetes (T1D). Interestingly, CTSH was identified as a protective factor for narcolepsy (p = 1.58E - 09) but a risk factor for T1D (p = 7.36E - 11), respectively. External validation supported the associations of eight of these proteins with three ADs.
Conclusions: Our integrated study identified 12 potential therapeutic targets for ADs and provided novel insights into future drug development for ADs.
期刊介绍：
Autoimmunity is an international, peer reviewed journal that publishes articles on cell and molecular immunology, immunogenetics, molecular biology and autoimmunity. Current understanding of immunity and autoimmunity is being furthered by the progress in new molecular sciences that has recently been little short of spectacular. In addition to the basic elements and mechanisms of the immune system, Autoimmunity is interested in the cellular and molecular processes associated with systemic lupus erythematosus, rheumatoid arthritis, Sjogren syndrome, type I diabetes, multiple sclerosis and other systemic and organ-specific autoimmune disorders. The journal reflects the immunology areas where scientific progress is most rapid. It is a valuable tool to basic and translational researchers in cell biology, genetics and molecular biology of immunity and autoimmunity.
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