Causal link between obesity and the risk of hypothyroidism: a two-sample Mendelian Randomization study

In some observational studies, a high-fat diet has been linked to an increased risk of hypothyroidism. However, the causal nature of these associations remains unclear. The aim of this study is to examine whether the association between body fat percentage and an increased risk of hypothyroidism is robust and potentially causal. We conducted a two-sample Mendelian randomization study to assess these associations. Instrumental variables related to exposure at the genome-wide significance level (P < 5 × 10–8) were derived from the IEU Open GWAS database, encompassing 454,633 individuals. Data on hypothyroidism were sourced from the same database, including 22,687 cases and 440,246 controls. The odds ratios (OR) for hypothyroidism were analyzed using various methods: MR Egger (OR = 1.027, 95% Confidence Interval (CI): 1.008–1.046, P = 3.7e-03), Weighted Median (OR = 1.024, 95% CI: 1.017–1.031, P = 7.06e-13), Inverse Variance Weighted (OR = 1.022, 95% CI: 1.016–1.028, P = 2.91e-14), Simple Mode (OR = 1.035, 95% CI: 1.005–1.065, P = 1.88e-02), and Weighted Mode (OR = 1.04, 95% CI: 1.010–1.070, P = 7.24e-03). This study supports the independent causal role of body fat percentage in the development of hypothyroidism.