{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T05:06:17Z","timestamp":1789103177347,"version":"build-2803163510"},"reference-count":26,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["RS-2024-00437038"],"award-info":[{"award-number":["RS-2024-00437038"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2024-00437038"],"award-info":[{"award-number":["RS-2024-00437038"]}],"id":[{"id":"https:\/\/ror.org\/00fdzyk40","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Observational studies in East Asia have not shown increased gastric cancer risk in ulcerative colitis, whereas a previous genetic analysis reported a positive association. Because both diseases have major histocompatibility complex (MHC) signals, we assessed whether the association was most apparent in MHC variants under ancestry-matched instrument selection. Methods: We performed a two-stage, two-sample Mendelian randomization study of 12 East Asian datasets (11 immune-related phenotypes) and a gastric cancer genome-wide association study (7921 cases; 159,201 controls), with instruments selected against the 1000 Genomes East Asian panel. For ulcerative colitis, we compared all, MHC, and non-MHC variants, evaluated signal overlap at HLA-DQA1\/DQB1, and assessed cross-disease specificity. Results: Ulcerative colitis was the only phenotype associated with gastric cancer after false-discovery-rate correction (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.09\u20131.24; q = 1.37 \u00d7 10\u22124). The MHC estimate was similar (OR 1.18, 95% CI 1.11\u20131.26), whereas the non-MHC estimate was close to 1 but rested on only two variants and remained imprecise (OR 1.00, 95% CI 0.86\u20131.17). The traits showed overlapping signals at HLA-DQA1\/DQB1, and the MHC variants were associated with several other immune diseases. Conclusions: The positive association was most apparent in MHC variants that were not specific to ulcerative colitis. The association therefore appears to be largely carried by pleiotropic MHC variants, although these data cannot establish the pathway that explains it.<\/jats:p>","DOI":"10.3390\/genes17091077","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T13:53:28Z","timestamp":1788789208000},"page":"1077","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["MHC-Related Shared Genetic Susceptibility Between Ulcerative Colitis and Gastric Cancer in East Asians"],"prefix":"10.3390","volume":"17","author":[{"given":"Ji Eun","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4271-7205","authenticated-orcid":false,"given":"Hyuk","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"},{"name":"Samsung Precision Genome Medicine Institute, Samsung Medical Center, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young Eun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae-Se","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang Won","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"},{"name":"Samsung Precision Genome Medicine Institute, Samsung Medical Center, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Hoon","family":"Min","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Haeng","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poong-Lyul","family":"Rhee","sequence":"additional","affiliation":[{"name":"Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Badr, M.T., Omar, M., and Hacker, G. (2021). Comprehensive Integration of Genome-Wide Association and Gene Expression Studies Reveals Novel Gene Signatures and Potential Therapeutic Targets for Helicobacter pylori-Induced Gastric Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.624117"},{"key":"ref_2","first-page":"283","article-title":"Atrophic gastritis of distinct etiologies: Malignant potential in Helicobacter pylori-associated and autoimmune forms","volume":"39","author":"Rokkas","year":"2026","journal-title":"Ann. Gastroenterol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"101404","DOI":"10.1016\/j.eclinm.2022.101404","article-title":"The current and future incidence and mortality of gastric cancer in 185 countries, 2020-40: A population-based modelling study","volume":"47","author":"Morgan","year":"2022","journal-title":"eClinicalMedicine"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1038\/s41416-024-02714-7","article-title":"Autoimmune conditions and gastric cancer risk in a population-based study in the United Kingdom","volume":"131","author":"Murphy","year":"2024","journal-title":"Br. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"103410","DOI":"10.1016\/j.eclinm.2025.103410","article-title":"Evaluating the risk of digestive system cancer in autoimmune disease patients: A systematic review and meta-analysis focusing on bias assessment","volume":"87","author":"Reizner","year":"2025","journal-title":"eClinicalMedicine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"841","DOI":"10.4143\/crt.2019.151","article-title":"Autoimmune Diseases and Gastric Cancer Risk: A Systematic Review and Meta-Analysis","volume":"51","author":"Song","year":"2019","journal-title":"Cancer Res. Treat."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Kim, H.M., Kim, J., Kim, H., Park, S.C., Lee, J.K., Kang, D.R., Kim, S.Y., and Kim, H.S. (2023). Risk of Gastric Cancer among Patients with Newly Diagnosed Ulcerative Colitis: A Nationwide Population-Based Study. J. Clin. Med., 12.","DOI":"10.3390\/jcm12082843"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wei, Q., Wang, Z., Liu, X., Liang, H., and Chen, L. (2023). Association between Gastric Cancer and 12 Autoimmune Diseases: A Mendelian Randomization Study. Genes, 14.","DOI":"10.3390\/genes14101844"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Yu, C., Xu, J., Xu, S., Tang, L., Han, Q., Zeng, X., Huang, Y., Yu, T., and Sun, Z. (2024). Exploring genetic associations of Crohn\u2019s disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1339207"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1038\/ng.3359","article-title":"Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations","volume":"47","author":"Liu","year":"2015","journal-title":"Nat. Genet."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1001\/jama.2021.18236","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: The STROBE-MR Statement","volume":"326","author":"Skrivankova","year":"2021","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41588-018-0336-0","article-title":"Genetic and phenotypic landscape of the major histocompatibilty complex region in the Japanese population","volume":"51","author":"Hirata","year":"2019","journal-title":"Nat. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e70098","DOI":"10.1111\/hel.70098","article-title":"Host Genetic Variants Associated With Helicobacter pylori Infection: A Meta-Analysis Combined With Functional Annotation","volume":"30","author":"Zhao","year":"2025","journal-title":"Helicobacter"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1038\/s41588-021-00931-x","article-title":"A cross-population atlas of genetic associations for 220 human phenotypes","volume":"53","author":"Sakaue","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"669","DOI":"10.1038\/s41588-020-0640-3","article-title":"Large-scale genome-wide association study in a Japanese population identifies novel susceptibility loci across different diseases","volume":"52","author":"Ishigaki","year":"2020","journal-title":"Nat. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"1000 Genomes Project Consortium, Auton, A., Brooks, L.D., Durbin, R.M., Garrison, E.P., Kang, H.M., Korbel, J.O., Marchini, J.L., McCarthy, S., and McVean, G.A. (2015). A global reference for human genetic variation. Nature, 526, 68\u201374.","DOI":"10.1038\/nature15393"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s10654-018-0424-6","article-title":"Mendelian randomization with a binary exposure variable: Interpretation and presentation of causal estimates","volume":"33","author":"Burgess","year":"2018","journal-title":"Eur. J. Epidemiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1002\/gepi.21965","article-title":"Consistent Estimation in Mendelian Randomization with Some Invalid Instruments Using a Weighted Median Estimator","volume":"40","author":"Bowden","year":"2016","journal-title":"Genet. Epidemiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int. J. Epidemiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","article-title":"Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases","volume":"50","author":"Verbanck","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Hemani, G., Tilling, K., and Davey Smith, G. (2017). Orienting the causal relationship between imprecisely measured traits using GWAS summary data. PLoS Genet., 13.","DOI":"10.1101\/117101"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Giambartolomei, C., Vukcevic, D., Schadt, E.E., Franke, L., Hingorani, A.D., Wallace, C., and Plagnol, V. (2014). Bayesian test for colocalisation between pairs of genetic association studies using summary statistics. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004383"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e34408","DOI":"10.7554\/eLife.34408","article-title":"The MR-Base platform supports systematic causal inference across the human phenome","volume":"7","author":"Hemani","year":"2018","journal-title":"eLife"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e13058","DOI":"10.1111\/hel.13058","article-title":"Helicobacter pylori antigens as immunomodulators of immune system","volume":"29","author":"Marzhoseyni","year":"2024","journal-title":"Helicobacter"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/gutjnl-2025-335823","article-title":"Asian Pacific Association of Gastroenterology task force recommendations on surveillance for Helicobacter pylori associated gastric premalignant conditions","volume":"75","author":"Leung","year":"2026","journal-title":"Gut"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3032","DOI":"10.1038\/s41467-025-58248-w","article-title":"A genome-wide cross-trait analysis characterizes the shared genetic architecture between lung and gastrointestinal diseases","volume":"16","author":"You","year":"2025","journal-title":"Nat. Commun."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1077\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T04:21:45Z","timestamp":1789100505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1077"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,7]]},"references-count":26,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091077"],"URL":"https:\/\/doi.org\/10.3390\/genes17091077","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,7]]}}}