GERD Diagnosis Significantly Increases Risk of Concomitant RA

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A comprehensive bidirectional Mendelian randomization (MR) analysis showed for the European population, gastroesophageal reflux disease (GERD) can influence the occurrence of rheumatoid arthritis (RA), although RA had no significant link to GERD, according to a study published in Frontiers in Genetics.¹ Results indicated patients with GERD are at a 69% increased risk of developing RA, underscoring its status as a substantial risk factor.

Approximately 1 out of 5 people in North America are diagnosed with GERD, a condition which is almost 4 times more prevalent when compared with Asian populations. The disease is characterized by symptoms including heartburn, nausea, inappetence, and a susceptibility to pharyngitis. It is caused by anatomy changes, such as hiatus musculature, an increase in the pressure gradient between the abdomen and thorax, and dysmotility of the esophagus.²

“In addition to anatomical and physiological factors, inflammation occurring in the stomach and esophagus plays a crucial role in the development of GERD,” wrote a group of Chinese investigators. “Consistently, an association between GERD and systemic inflammatory diseases has been reported, particularly for RA.”

As the link between GERD and RA has been reported by previous observational studies in Asia, the study used genetic evidence to examine the bidirectional causal effects between the 2 conditions. Two MR analyses were conducted using data from 129,090 patients with GERD and 602,604 controls, of which 6236 patients with GERD had concomitant RA compared with 147,221 controls.

The primary analysis was the inverse-variance weighted (IVW) method, while supplementary analyses were weighted median and MR-Egger regression. Heterogeneity was determined using the Cochran’s Q test. Other multivariable analyses were performed to exclude any confounding factors, such as body mass index, time spent watching television, and years of schooling between GERD and RA.

Results showed GERD influenced the occurrence of RA (odds ratio [OR] = 1.69, P <.00125). Both univariate MR (UVMR) and multivariable MR (MVMR) demonstrated a causal and positive influence between GERD and RA (UVMR: OR = 1.49, 95% confidence interval [CI] = 1.25 – 1.76, P = 6.18*10−6; MVMR: OR = 1.69, 95% CI = 1.24 – 2.31, P = 8.62*10−4). However, RA had no such influence on GERD diagnosis (UVMR: OR = 1.03, 95% CI = 1.00 – 1.06, P = .042; MVMR: OR = 1.04, 95% CI = 1.00 – 1.07, P = .0271). According to the Cochran’s Q test, heterogeneity was not classified as the effect of GERD on RA (P = .794).

After the removal of confounding factors, the causal relationship of GERD on RA still existed (OR = 1.69, 95% CI = 1.24 – 2.31, P <.0125), which was consistent with UVMR. Although the years of schooling was deemed an effective protective factor for GERD (OR = .36, 95% CI = .31 – .41, P <.0125), body mass index (OR = 1.27, 95% CI = 1.18 – 1.37, P <.0125) and time spent watching television (OR = 1.72, 95% CI = 1.33 – 2.24, P< .0125) were risk factors for GERD.

Investigators noted limitations including using data from European participants, although most prior research focused on Asian subjects. Therefore, whether the results are generalizable to non-European populations need to be confirmed in future studies. Additionally, newer and more extensive data may produce different findings.

“Our bidirectional MR analysis found that for the European population, GERD can induce the occurrence of RA, whereas RA only has no significant influence on GERD,” wrote investigators.

References

1. ^{Wang H, Chen Z, Dang X, Wang H. Rheumatoid arthritis and gastroesophageal reflux disease: a bidirectional and multivariable two-sample Mendelian randomization study. Front Genet. 2023;14:1280378. Published 2023 Dec 13. doi:10.3389/fgene.2023.1280378}
2. ^{Punjabi, P., Hira, A., Prasad, S., Wang, X., and Chokhavatia, S. (2015). Review of gastroesophageal reflux disease (GERD) in the diabetic patient. J. Diabetes 7, 599–609. doi:10.1111/1753-0407.12279}