Abstract
The etiology of non-alcoholic fatty liver disease (NAFLD) involves complex interaction of genetic and environmental factors. A large number of observational studies have shown that hypothyroidism contributes to a high risk of NAFLD. However, the exact causality is still unknown. Due to the progress of genome-wide association study (GWAS) and the discovery of Mendelian randomization (MR), it is possible to explore the causality between the two diseases. In this study, in order to research into the influence of intermediate phenotypes on outcome, nine independent genetic variants of hypothyroidism obtained from the GWAS were used as instrumental variables (IVs) to perform MR analysis on NAFLD. Since there was no heterogeneity between IVs (P = 0.70), a fixed-effects model was used. The correlation between hypothyroidism and NAFLD was evaluated by using inverse-variance weighted (IVW) method and weighted median method. Then the sensitivity test was analyzed. The results showed that there was a high OR (1.7578; 95%CI 1.1897-2.5970; P = 0.0046) and a low intercept (-0.095; P = 0.431). None of the genetic variants drove the overall result (P < 0.01). Simply, we proved for the first time that the risk of NAFLD increases significantly on patients with hypothyroidism. Furthermore, we explained possible causes of NAFLD caused by hypothyroidism.