{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T15:15:39Z","timestamp":1789139739224,"version":"build-2803163510"},"reference-count":78,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":58,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82273704"],"award-info":[{"award-number":["82273704"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82504482"],"award-info":[{"award-number":["82504482"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Helicobacter"],"published-print":{"date-parts":[[2025,11]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background and Aims<\/jats:title>\n \n \n Helicobacter pylori<\/jats:italic>\n <\/jats:styled-content>\n (\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n ) is a major risk factor for gastric cancer (GC) and multiple other chronic illnesses. Host genetic factors influence the susceptibility to\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n infection, as evidenced by elevated concordance in monozygotic twins and racial disparities independent of socioeconomic status. Leveraging meta\u2010analyses and\n in silico<\/jats:italic>\n functional annotation, we investigated host genetic susceptibility to\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n infection, and to examine how these variants may influence gastric cancer (GC) risk.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Meta\u2010analyses were performed on 25 candidate genetic variants that had been investigated for the association with\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n infection in at least three studies, under five genetic models (allelic, dominant, recessive, homozygous, and heterozygous). Meta\u2010analyses on genome\u2010wide variants were conducted using the allelic model. The Bayesian False\u2010Discovery Probability method and Venice criteria were used to assess genetic association credibility. The Genotype\u2010Tissue Expression (GTEx) and eQTLGen databases were used for cis\u2010expression quantitative trait locus (eQTL) analysis. Differential gene expression in\n \n H.\u00a0pylori<\/jats:italic>\n <\/jats:styled-content>\n \u2010positive (\n n<\/jats:italic>\n \u2009=\u200961) vs. \u2010negative (\n n<\/jats:italic>\n \u2009=\u200917) samples, and GC (\n n<\/jats:italic>\n \u2009=\u2009414) vs. non\u2010GC tissues (\n n<\/jats:italic>\n \u2009=\u2009210) was analyzed leveraging The Cancer Genome Atlas, GTEx, and in\u2010house RNA\u2010sequencing data.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n From a total of 103 studies for systematic review, meta\u2010analyses based on 83 studies identified 47 variants across 18 loci associated with\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n susceptibility. These loci encompassed 29 cis\u2010eQTLs affecting expression of 42 genes. Of them, seven genes at three loci\u20144p14 (\n TLR10<\/jats:italic>\n ,\n TLR6<\/jats:italic>\n ,\n KLHL5<\/jats:italic>\n ,\n TMEM156<\/jats:italic>\n ), 6p21.33 (\n HLA\u2010DRB6<\/jats:italic>\n ,\n C4B<\/jats:italic>\n ), and 14q32.2 (\n WARS<\/jats:italic>\n )\u2014were consistently upregulated in\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n infection and GC, which may contribute to\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n infection\u2010related GC development.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Host genetic predisposition alters the odds of\n \n H. pylori<\/jats:italic>\n <\/jats:styled-content>\n infection, demonstrating the importance of host\u2010pathogen crosstalk in infection dynamics and subsequent gastric carcinogenesis.\n <\/jats:p>\n 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