Multi-Systemic Disease Associations of Gastrin: A Proteogenomic Analysis of 396 Health-Related Outcomes

Multi-Systemic Disease Associations of Gastrin: A Proteogenomic Analysis of 396 Health-Related Outcomes | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL British Journal of Pharmacology This is a preprint and has not been peer reviewed. Data may be preliminary. 12 May 2026 V1 Latest version Share on Multi-Systemic Disease Associations of Gastrin: A Proteogenomic Analysis of 396 Health-Related Outcomes Authors : Han Zhang [email protected] , Lingyi Li [email protected] , Zheng Li [email protected] , Wentao Huang [email protected] , Yan Qin [email protected] , Weixiang Guan [email protected] , Yanlin Lyu [email protected] , … Show All … , Zuodi Liang [email protected] , Ruijie Zeng [email protected] , Jing Feng [email protected] , Zixun Li [email protected] , Yajie Zhang [email protected] , Shiyi Yu [email protected] , Wanyi Liu [email protected] , Dongling Luo [email protected] , Felix W Leung [email protected] , Weihong Sha [email protected] , Junqing Xie [email protected] , and Hao Chen 0000-0003-4339-3441 [email protected] Show Fewer Authors Info & Affiliations https://doi.org/10.22541/authorea.15003081/v1 19 views 5 downloads Contents Abstract Graphical Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Gastrin (GAST) is a gastrointestinal hormone characterized by promoting gastric acid secretion and gastric mucosal growth, and its potential effects on other systems are of increasing interest. However, most studies on GAST have focused on digestive disorders, while its associations with multi-systemic diseases remains to be explored. Methods: We examined associations between GAST and 328 common diseases, 46 rare diseases and 22 death outcomes using the UK Biobank. GAST were analyzed using multivariate Cox proportional hazards models. Bonferroni correction was used to minimize false-positive results. In addition, polygenic risk score (PRS)-based phenotype-wide association analysis (PheWAS) was used to explore the association between GAST-PRS and disease phenotypes. Linkage disequilibrium score regression analyzed GAST -disease genetic correlations. Findings: After multiple corrections, GAST showed positive multi-systemic associations spanning 152 common diseases (vitamin B12 deficiency anaemia Hazard Ratios (HR) 1.85 [95% Confidence Interval (CI) 1.68–2.02]; P =2.28×1 0 -39 )), 10 rare diseases(systemic lupus erythematosus HR 1.68 [95% CI 1.47-1.92]; P =4.08×1 0 -14 ), and 8 death outcomes(death due to heart failure HR 1.50 [95% CI 1.20-1.90]; P =3.10×1 0 -4 ). PRS-PheWAS results indicated higher GAST-PRS was associated with a higher risk of developing 54 diseases. There was a positive genetic correlation between GAST and the development of 6 diseases. Interpretation: GAST demonstrated multi-systemic associations with morbidity and mortality across 168 disease outcomes, challenging the classical paradigm of its gastrointestinal-specific functions. These findings established GAST as a multi-system risk indicator, supporting its potential utility for risk stratification while requiring further mechanistic investigation. 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Information & Authors Information Version history V1 Version 1 12 May 2026 Collection British Journal of Pharmacology Authors Affiliations Han Zhang [email protected] View all articles by this author Lingyi Li [email protected] View all articles by this author Zheng Li [email protected] View all articles by this author Wentao Huang [email protected] View all articles by this author Yan Qin [email protected] South China University of Technology School of Medicine, Guangzhou, China, 510006 View all articles by this author Weixiang Guan [email protected] View all articles by this author Yanlin Lyu [email protected] View all articles by this author Zuodi Liang [email protected] View all articles by this author Ruijie Zeng [email protected] South China University of Technology School of Medicine, Guangzhou, China, 510006 View all articles by this author Jing Feng [email protected] View all articles by this author Zixun Li [email protected] View all articles by this author Yajie Zhang [email protected] View all articles by this author Shiyi Yu [email protected] View all articles by this author Wanyi Liu [email protected] View all articles by this author Dongling Luo [email protected] South China University of Technology School of Medicine, Guangzhou, China, 510006 View all articles by this author Felix W Leung [email protected] View all articles by this author Weihong Sha [email protected] View all articles by this author Junqing Xie [email protected] South China University of Technology School of Medicine, Guangzhou, China, 510006 View all articles by this author Hao Chen 0000-0003-4339-3441 [email protected] View all articles by this author Metrics & Citations Metrics Article Usage 19 views 5 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Han Zhang, Lingyi Li, Zheng Li, et al. Multi-Systemic Disease Associations of Gastrin: A Proteogenomic Analysis of 396 Health-Related Outcomes. Authorea . 12 May 2026. DOI: https://doi.org/10.22541/authorea.15003081/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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