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World J Methodol. Sep 20, 2026; 16(3): 117891
Published online Sep 20, 2026. doi: 10.5662/wjm.117891
Functional dyspepsia and risk of Barrett’s esophagus and dysplasia: A propensity-matched multicenter retrospective cohort study
Muhammad Hassaan Arif Maan, Soban Maan, Muhammad Waleed, Muhammad Mursaleen Ahmad, Ritik Mahaveer Goyal, Amir Humza Sohail, Yazan Abboud, Sunnia Khan, Swapna Gayam, Justin Kupec
Muhammad Hassaan Arif Maan, Ritik Mahaveer Goyal, Yazan Abboud, Department of Medicine, Rutgers New Jersey Medical School, Newark, NJ 07103, United States
Soban Maan, Muhammad Waleed, Swapna Gayam, Justin Kupec, Department of Medicine, Division of Gastroenterology and Hepatology, West Virginia University, Morgantown, WV 26506, United States
Muhammad Mursaleen Ahmad, Department of Medicine, Pakistan Institute of Medical Sciences, Islamabad 44010, Pakistan
Amir Humza Sohail, Department of Surgery, University of New Mexico, Albuquerque, NM 87106, United States
Sunnia Khan, Department of Medicine, Punjab Medical College, Faisalabad 38000, Punjab, Pakistan
Author contributions: Maan MHA and Maan S conceptualized and designed the study, performed data extraction and analysis, and drafted the manuscript; Waleed M and Ahmad MM assisted with data curation and literature review, along with manuscript writing; Goyal RM, Abboud Y, and Khan S supported the methodology section, critically reviewed, and edited the manuscript; Sohail AH contributed to the discussion, critically reviewed, and edited the manuscript; Gayam S and Kupec J supervised the study and provided critical revisions. All authors reviewed and approved the final manuscript.
AI contribution statement: “OpenEvidence” is an AI-based medical knowledge assistance tool that was used during the writing of this paper. It was only employed within a limited scope to streamline and condense the author's written text to make it more concise, mainly in the abstract and conclusion sections. This tool was not used for generating new content, conducting data analysis, or performing translation. All scientific content, structure, and conclusions were entirely created by the author.
Institutional review board statement: Because this study utilized de-identified data from the TriNetX research network, it was exempt from institutional review board approval in accordance with 45 CFR 46.101(b)(4).
Informed consent statement: Informed consent was waived because the study involved only the analysis of fully de-identified data obtained from the TriNetX research network.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
Corresponding author: Muhammad Hassaan Arif Maan, MD, Department of Medicine, Rutgers New Jersey Medical School, Stadium Road, Newark, NJ 07103, United States.
m.hassaanmaan@gmail.com
Received: December 18, 2025
Revised: January 17, 2026
Accepted: March 2, 2026
Published online: September 20, 2026
Processing time: 204 Days and 7.9 Hours
BACKGROUND
Functional dyspepsia (FD) and gastroesophageal reflux disease (GERD) exhibit substantial symptom overlap (40%-50%), and up to one-third of patients diagnosed with FD demonstrate pathologic acid exposure on objective testing. While GERD is a well-established risk factor for Barrett’s esophagus (BE), the association between FD diagnosis and BE risk remains unexplored. Understanding this relationship is critical because FD is typically diagnosed symptomatically without routine objective reflux testing in clinical practice, potentially masking undiagnosed GERD or identifying shared pathophysiologic mechanisms. We hypothesized that patients diagnosed with FD demonstrate an elevated risk for BE and Barrett’s-associated dysplasia compared to matched controls.
AIM
To investigate the association between FD diagnosis and the risk of BE and dysplasia.
METHODS
This retrospective cohort study utilized the TriNetX Global Collaborative Network database. Patients diagnosed with FD (International Classification of Diseases, 10th Revision code K30) between January 2006 and December 2022 were identified, and propensity-score matched 1:1 with controls based on demographics, comorbidities, and GERD diagnosis. The primary outcomes were the development of BE and Barrett’s-associated dysplasia. Cox proportional hazards regression analysis was performed to calculate hazard ratios (HR) with 95% confidence intervals (CI). A sensitivity analysis was conducted to include patients with documented esophagoduodenoscopy during the study period.
RESULTS
After PSM, 384267 patients were included in each cohort. Patients with FD demonstrated significantly higher risk for BE (HR: 1.900, 95%CI: 1.813-1.991), Barrett's associated dysplasia (HR: 3.568, 95%CI: 3.064-4.155), and esophageal cancer (HR: 1.649, 95%CI: 1.450-1.875). Sensitivity analysis confirmed the increased risk of BE and dysplasia but not esophageal cancer.
CONCLUSION
Patients diagnosed with FD demonstrate substantially elevated risk for BE and dysplasia. This association, whether reflecting undiagnosed GERD, shared pathophysiology, or both, identifies FD patients as a higher-risk population warranting consideration of objective reflux testing and selective endoscopic evaluation in appropriate clinical contexts.
Core Tip: This large-scale cohort study of over 3.6 million patients demonstrates that individuals diagnosed with functional dyspepsia (FD) have a substantially elevated risk for Barrett's esophagus and dysplasia compared to matched controls. Interestingly, this increased risk persisted even after adjusting for documented gastroesophageal reflux disease (GERD). Whether this reflects true pathophysiologic overlap, diagnostic misclassification (especially considering overlap in presentation for FD and gastroesophageal reflux disease), or shared predisposing factors, patients diagnosed with FD represent a higher-risk population warranting reconsideration of current diagnostic strategies, including objective reflux testing and risk-stratified endoscopic evaluation.
