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Objective <p>Observational studies have linked gastroesophageal reflux disease (GERD) to various otolaryngologic diseases (ear, nose, and throat [ENT] disorders), but causal inference is limited by confounding and reverse causation. We used Mendelian randomization (MR) to evaluate causality while minimizing these biases.</p> Methods <p>MR analyses were conducted using genome-wide association study (GWAS) data from individuals of European ancestry. GERD data were derived from a meta-analysis of UK Biobank and QSKIN (<i>N</i> = 602,604; cases = 129,080), and outcome data were obtained from FinnGen (outcome sample sizes ranged from 157,453 to 404,309). Six complementary MR methods (including IVW and MR-Egger) were applied to assess the causal effect of GERD on seven otolaryngologic diseases: allergic rhinitis (AR), chronic sinusitis (CRS), nasal polyps (NP), vocal cord dysfunction (VCD), sudden idiopathic hearing loss (SIHL), head and neck cancer (HNC), and thyroid carcinoma (THCA). After harmonization, the number of SNPs included in the analyses varied across outcomes, ranging from 65 to 75. Sensitivity analyses, including tests for heterogeneity, multiplicity, and leave-one-out analysis, were conducted to ensure robustness of the results.</p> Results <p>GERD was causally associated with an increased risk of AR–OR 1.17(95% CI 1.05–1.30), CRS–OR 1.25(95% CI 1.15–1.37), VCD–OR 1.52(95% CI 1.31–1.77), and SIHL–OR 1.38(95% CI 1.14–1.67). No causal effect was found for NP–OR 1.09(95% CI 0.95–1.25), HNC–OR 1.13(95% CI 0.90–1.42), or THCA–OR 1.07 (95% CI 0.83–1.39).</p> Conclusion <p>These results provide genetic evidence supporting a causal association between GERD and increased risks of AR, CRS, VCD, and SIHL. If validated in further studies, improved GERD prevention and management strategies could potentially reduce these risks.</p>

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Causal effects of GERD on ENT disorders: a Mendelian randomization study

  • 期刊论文

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  • 发表日期：

    2026年3月1日

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  • Heng Zhao,
  • Xiuli Ma,
  • Dan Song,
  • Xi Dai,
  • Yanli Qu,
  • Ruixue Zong,
  • Jing Ma

摘要

Objective

Observational studies have linked gastroesophageal reflux disease (GERD) to various otolaryngologic diseases (ear, nose, and throat [ENT] disorders), but causal inference is limited by confounding and reverse causation. We used Mendelian randomization (MR) to evaluate causality while minimizing these biases.

Methods

MR analyses were conducted using genome-wide association study (GWAS) data from individuals of European ancestry. GERD data were derived from a meta-analysis of UK Biobank and QSKIN (N = 602,604; cases = 129,080), and outcome data were obtained from FinnGen (outcome sample sizes ranged from 157,453 to 404,309). Six complementary MR methods (including IVW and MR-Egger) were applied to assess the causal effect of GERD on seven otolaryngologic diseases: allergic rhinitis (AR), chronic sinusitis (CRS), nasal polyps (NP), vocal cord dysfunction (VCD), sudden idiopathic hearing loss (SIHL), head and neck cancer (HNC), and thyroid carcinoma (THCA). After harmonization, the number of SNPs included in the analyses varied across outcomes, ranging from 65 to 75. Sensitivity analyses, including tests for heterogeneity, multiplicity, and leave-one-out analysis, were conducted to ensure robustness of the results.

Results

GERD was causally associated with an increased risk of AR–OR 1.17(95% CI 1.05–1.30), CRS–OR 1.25(95% CI 1.15–1.37), VCD–OR 1.52(95% CI 1.31–1.77), and SIHL–OR 1.38(95% CI 1.14–1.67). No causal effect was found for NP–OR 1.09(95% CI 0.95–1.25), HNC–OR 1.13(95% CI 0.90–1.42), or THCA–OR 1.07 (95% CI 0.83–1.39).

Conclusion

These results provide genetic evidence supporting a causal association between GERD and increased risks of AR, CRS, VCD, and SIHL. If validated in further studies, improved GERD prevention and management strategies could potentially reduce these risks.