Genetically Predicted Gastroesophageal Reflux Disease and Common Thyroid Disorders: A Two-sample Mendelian Randomization Study.

INTRODUCTION

The causality between thyroid disorders and Gastroesophageal Reflux Disease (GERD) remains to be deciphered. This two-sample Mendelian Randomization (MR) study was performed to elucidate the causal association between GERD and thyroid diseases and functions.

METHODS

Summary statistics for GERD were retrieved from a published GWAS dataset deposited in the Integrative Epidemiology Unit OpenGWAS database. Thyroid hormone level data were obtained from the ThyroidOmics Consortium, and genetic variants associated with thyroid disorders were sourced from the FinnGen Project. MR statistical analyses used the Inverse Variance Weighted (IVW) algorithm, followed by various sensitivity and reliability analyses. Odds Ratio (OR) and beta coefficient (β) with 95% Confidence Interval (CI) were estimated for categorical and continuous outcomes, respectively. The significant causal association was determined based on a Bonferroni-corrected threshold of p-value < 0.0021 (calculated as 0.05/24 trait pairs).

RESULTS

The findings of MR analysis tend to favor the causality of GERD for hyperthyroidism (IVW: OR = 1.517, 95% CI: 1.164 to 1.978, p = 2.04E-03) but not the other thyroid disorders. The reverse MR estimates suggested that thyroid disorders may not affect the susceptibility of GERD. Moreover, genetic proxied GERD was significantly negatively associated with circulating Thyroid Stimulating Hormone (TSH) level (IVW: β = -0.048, 95% CI: -0.078 to -0.019, p = 1.17E-03), whereas the causality of this enteropathy on Free Triiodothyronine (FT3), Free Thyroxine (FT4), Total Triiodothyronine (TT3), FT3/FT4 ratio, and TT3/FT4 ratio (and vice versa) is unfounded.

DISCUSSION: This MR study indicates that the genetic liability to GERD is significantly detrimental to hyperthyroidism risk and the homeostasis of TSH.

CONCLUSION

The findings suggest that effective GERD management could mitigate hyperthyroidism risk.