AccScience Publishing / JCTR / Online First / DOI: 10.36922/JCTR026050009
ORIGINAL ARTICLE

Stomach disease as a terminal node in comorbidity networks among middle-aged and older adults: An integrated analysis of network topology and risk factors

Linya Lyu1 Wei Fu1* Fang Dai1 Jinji Huang1 Guobin Cheng1
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1 Department of Gastroenterology, The 925th Hospital of PLA Joint Logistics Support Force, Guiyang, Guizhou, China
Received: 29 January 2026 | Revised: 31 March 2026 | Accepted: 14 April 2026 | Published online: 16 June 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Background: Stomach disease is highly prevalent among middle-aged and older adults and often coexists with other chronic conditions, yet its comorbidity patterns remain unclear. This cross-sectional study aimed to construct a comorbidity network for stomach disease and identify its key associated factors using data from the China Health and Retirement Longitudinal Study (CHARLS, 2008–2020). Methods: A total of 19,541 participants were included. Data on 18 demographic variables and 14 chronic diseases were collected. Disease network analysis, extended Bayesian information criterion graphical least absolute shrinkage and selection operator (LASSO), the LASSO regression, and logistic regression were employed to examine network topology and factors associated with stomach disease. Results: A total of 19,541 unique participants were included. Among them, 26.17% (5,114/19,541) had stomach disease. Disease network analysis and regression analysis revealed significant, stable relationships among the included diseases. Nine diseases, including arthritis, dyslipidemia, and heart disease, were identified as independent factors associated with stomach disease. Among demographic characteristics, nine indicators, such as age, male sex, and current alcohol consumption, were independently associated with stomach disease (p < 0.05). Conclusion: Our study reveals that stomach disease in middle-aged and older adults primarily functions as a “terminal” phenomenon. It is statistically associated with core diseases within the network. Stomach disease is independently associated with multiple chronic conditions, such as arthritis, heart disease, and liver diseases, as well as factors like rural residence. These associations should be interpreted as statistical correlations rather than causal relationships, given the cross-sectional design. Relevance for patients: Stomach disease in older adults often reflects broader chronic disease burdens, warranting holistic rather than symptom-only management.

Keywords
Stomach disease
Middle-aged and older adults
CHARLS
Disease network analysis
Funding
This study was supported by funding from the Science Foundation of the 925th Hospital (No. 2025[3]).
Conflict of interest
The authors declare no competing interests.
References
  1. Liu Y, Zhang J, Guo Y, et al. Global burden and risk factors of gastritis and duodenitis: an observational trend study from 1990 to 2019. Sci Rep. 2024;14(1):2697. doi: 10.1038/s41598-024-52936-1
  2. Wang L, Jiang W, Li H. Global, regional, and national burden of gastritis and duodenitis from 1990 to 2021 with projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021. Int J Med Sci. 2025;22(11):2570-2582. doi: 10.7150/ijms.109762
  3. Qiao X, Chen X, Wang W, Guo L, Pan Q. Classification of Elderly Patients with Comorbidities and Their Subtypes: A Data-Driven Cluster Analysis. Clin Interv Aging. 2025;20:1671-1680. doi: 10.2147/CIA.S549148
  4. Bezerra de Souza DL, Oliveras-Fabregas A, Espelt A, et al. Multimorbidity and its associated factors among adults aged 50 and over: A cross-sectional study in 17 European countries. PLoS ONE. 2021;16(2):e0246623. doi: 10.1371/journal.pone.0246623
  5. Zhang Q, Han X, Zhao X, Wang Y. Multimorbidity patterns and associated factors in older Chinese: results from the China health and retirement longitudinal study. BMC Geriatr. 2022;22(1):470. doi: 10.1186/s12877-022-03154-9
  6. Jiang F, Wang L, Ying H, et al. Multisystem health comorbidity networks of metabolic dysfunction-associated steatotic liver disease. Medicine. 2024;5(11):1413-23.e3. doi: 10.1016/j.medj.2024.07.013
  7. Zhao Y, Hu Y, Smith JP, Strauss J, Yang G. Cohort profile: the China Health and Retirement Longitudinal Study (CHARLS). Int J Epidemiol. 2014;43(1):61-68. doi: 10.1093/ije/dys203
  8. Zhang Z, Hu C, Cai Y, et al. The evolution of comorbidities in chronic diseases among Chinese middle-aged and elderly people: Evidence from the CHARLS (2015-2020). PLoS ONE. 2025;20(8):e0329372. doi: 10.1371/journal.pone.0329372
  9. Watts DJ, Strogatz SH. (1998). Collective Dynamics of » Small- World « Networks. Nature 393, S. 440–442. In: Schlüsselwerke der Netzwerkforschung. Springer Fachmedien Wiesbaden. 2018:551-553. doi: 10.1007/978-3-658-21742-6_130
  10. Avalos M, Pouyes H, Grandvalet Y, et al. Sparse conditional logistic regression for analyzing large-scale matched data from epidemiological studies: a simple algorithm. BMC Bioinform. 2015;16 Suppl 6: S1. doi: 10.1186/1471-2105-16-S6-S1
  11. Chen J, Yuan S, Fu T, et al. Gastrointestinal Consequences of Type 2 Diabetes Mellitus and Impaired Glycemic Homeostasis: A Mendelian Randomization Study. Diabetes Care. 2023;46(4):828-835. doi: 10.2337/dc22-1385
  12. Shao W, Zhang Y, Kong Y, et al. Multimorbidity profiles in patient population from Central China: a study based on electronic health records. Sci Bull. 2025:70(22):3840-3849. doi: 10.1016/j.scib.2025.10.019
  13. He J, Liu Y, Ouyang Q, et al. Helicobacter pylori and unignorable extragastric diseases: Mechanism and implications. Front Microbiol. 2022;13:972777. doi: 10.3389/fmicb.2022.972777
  14. Chen Y, Wang Y, Ni B, Ying G, Zhang J. Relationship between Helicobacter pylori and hypertriglyceridemia in the population. J Clin Lipidol. 2025;19(3):461-467. doi: 10.1016/j.jacl.2025.03.002
  15. Ye L, Yan K, Tian Z, et al. Helicobacter pylori infection is linked to metabolic dysfunction and associated steatotic liver disease: A large cross-sectional study. World J Gastroenterol. 2025;31(13):102563. doi: 10.3748/wjg.v31.i13.102563
  16. Narayanan SP, Anderson B, Bharucha AE. Sex- and Gender-Related Differences in Common Functional Gastroenterologic Disorders. Mayo Clin Proc. 2021;96(4):1071-1089. doi: 10.1016/j.mayocp.2020.10.004
  17. Prusator DK, Greenwood-Van Meerveld B. Amygdala-mediated mechanisms regulate visceral hypersensitivity in adult females following early life stress: importance of the glucocorticoid receptor and corticotropin-releasing factor. Pain. 2017;158(2):296-305. doi: 10.1097/j.pain.0000000000000759
  18. Benson S, Siebert C, Koenen LR, et al. Cortisol affects pain sensitivity and pain-related emotional learning in experimental visceral but not somatic pain: a randomized controlled study in healthy men and women. Pain. 2019;160(8):1719-1728. doi: 10.1097/j.pain.0000000000001579
  19. Yuan S, Chen J, Ruan X, et al. Smoking, alcohol consumption, and 24 gastrointestinal diseases: Mendelian randomization analysis. eLife. 2023;12:e84051. doi: 10.7554/eLife.84051
  20. Yang H, Zhang M, Li H, et al. Prevalence of common upper gastrointestinal diseases in Chinese adults aged 18-64 years. Sci Bull. 2024;69(24):3889-3898. doi: 10.1016/j.scib.2024.07.048
  21. Varghese S, Rao S, Khattak A, Zamir F, Chaari A. Physical Exercise and the Gut Microbiome: A Bidirectional Relationship Influencing Health and Performance. Nutrients. 2024;16(21):3663. doi: 10.3390/nu16213663
  22. Motiani KK, Collado MC, Eskelinen JJ, et al. Exercise Training Modulates Gut Microbiota Profile and Improves Endotoxemia. Med Sci Sports Exerc. 2020;52(1):94-104. doi: 10.1249/MSS.0000000000002112
  23. Paluch AE, Boyer WR, Franklin BA, et al. Resistance Exercise Training in Individuals With and Without Cardiovascular Disease: 2023 Update: A Scientific Statement From the American Heart Association. Circulation. 2024;149(3):e217-e231. doi: 10.1161/CIR.0000000000001189
  24. Zhou J, Li J, Chen J, et al. Decoding inflammatory mediators in the Correa’s cascade: From chronic gastritis to carcinogenesis and targeted therapies. Int Immunopharmacol. 2025;162:115191. doi: 10.1016/j.intimp.2025.115191
  25. Chen L, Zhu G, She L, Ding Y, Yang C, Zhu F. Analysis of Risk Factors and Establishment of a Prediction Model for Endoscopic Primary Bile Reflux: A Single-Center Retrospective Study. Front Med. 2021;8:758771. doi: 10.3389/fmed.2021.758771
  26. Marrache MK, Bou Daher H, Rockey DC. The relationship between portal hypertension and portal hypertensive gastropathy. Scand J Gastroenterol. 2022;57(3):340-344. doi: 10.1080/00365521.2021.2012591
  27. Fang J, Yu CH, Li XJ, et al. Gut dysbiosis in nonalcoholic fatty liver disease: pathogenesis, diagnosis, and therapeutic implications. Front Cell Infect Microbiol. 2022;12:997018. doi: 10.3389/fcimb.2022.997018
  28. Tilg H, Adolph TE, Trauner M. Gut-liver axis: Pathophysiological concepts and clinical implications. Cell Metab. 2022;34(11):1700-1718. doi: 10.1016/j.cmet.2022.09.017
  29. Zaher A, ElSaygh J, Midani A, et al. A Closer Look into Gastrointestinal Bleeding in Heart Failure Patients. Curr Probl Cardiol. 2024;49(9):102739. doi: 10.1016/j.cpcardiol.2024.102739
  30. Kamada T, Satoh K, Itoh T, et al. Evidence-based clinical practice guidelines for peptic ulcer disease 2020. J Gastroenterol. 2021;56(4):303-322. doi: 10.1007/s00535-021-01769-0
  31. García Agudo R, Aoufi Rabih S, González Carro P, et al. Gastrointestinal lesions in chronic kidney disease patients with anaemia. Nefrologia. 2019;39(1):50-57. doi: 10.1016/j.nefro.2018.05.010
  32. Wu T, Zhang L, Tian J, et al. Correlation between dyslipidaemia and gastric cancer: pathogenesis to prevention and treatment strategies. Lipids Health Dis. 2025;24(1):204. doi: 10.1186/s12944-025-02625-3
  33. Benenson I, Waldron FA, Jadotte YT, Dreker MP, Holly C. Risk factors for hypertensive crisis in adult patients: a systematic review. JBI Evid Synth. 2021;19(6):1292-1327. doi: 10.11124/JBIES-20-00243
  34. Yong H, Ganesh A, Camara-Lemarroy C. Gastrointestinal Dysfunction in Stroke. Semin Neurol. 2023;43(4):609-625. doi: 10.1055/s-0043-1771470
  35. Chiu YC, Chang WP, Tang GJ, Lan TY, Lee KY, Su VY. Chronic obstructive pulmonary disease is associated with a higher risk of functional gastrointestinal disorders. Respir Med. 2022;197:106833. doi: 10.1016/j.rmed.2022.106893
  36. Telesford QK, Joyce KE, Hayasaka S, et al. The ubiquity of small-world networks. Brain Connect. 2011;1(5):367-75. doi: 10.1089/brain.2011.0038
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Journal of Clinical and Translational Research, Electronic ISSN: 2424-810X Print ISSN: 2382-6533, Published by AccScience Publishing