Association of thyroid disease and risk of fatty liver disease: an exposure-wide Mendelian randomization study.

OBJECTIVE: Previous studies have often observed a possible association between thyroid and fatty liver diseases. The pathogenesis of both diseases is complex, with many confounding factors and controversies. We used a two-sample Mendelian randomization (MR) analysis to test the causality between thyroid disease and the risk of developing fatty liver disease.

MATERIALS AND METHODS: All data were obtained from the genome-wide association studies (GWAS) Catalog database. Thyroid disorders include hypothyroidism, hyperthyroidism, autoimmune thyroiditis, and Hashimoto's thyroiditis. Fatty liver diseases include alcoholic fatty liver disease and non-alcoholic fatty liver disease (NAFLD). The inverse variance weighting (IVW) method was used for MR analysis, and sensitivity analysis was further performed to test its robustness.

RESULTS: We discovered no causal relationship between thyroid disease and alcoholic fatty liver disease after excluding weak instrumental variables (IVs). Hyperthyroidism and hypothyroidism had a significant causal relationship with NAFLD. Hypothyroidism increased the risk of NAFLD using the IVW method (OR=7.62, 95% CI: 2.61-22.25, p<0.001). MR-Egger regression did not suggest potential evidence of directional pleiotropy (intercept, p=0.698). Hyperthyroidism also significantly increased the risk of NAFLD (OR=11.83, 95% CI: 2.9-22.54, p=0.026). MR-Egger regression did not suggest any potential directional pleiotropy (intercept, p=0.295).

CONCLUSIONS: Hypothyroidism can significantly increase NAFLD incidence, and hyperthyroidism may be a risk factor for NAFLD.