Hypothyroidism and glioblastoma risk: a two-sample Mendelian randomization study.
BACKGROUND: Prior observational evidence suggests a potential link between hypothyroidism and glioblastoma (GBM) risk. To investigate causality, we conducted a two-sample Mendelian randomization (MR) study. METHODS: Between April 2025 and July 2025, we leveraged summary - level data from European - ancestry genome-wide association studies (GWAS). The inverse - variance weighted (IVW) approach served as the primary method for causal inference. Robustness was evaluated using four complementary Mendelian randomization (MR) techniques: MR-Egger techniques: MR-Egger, weighted median (WM), weighted mode, and simple mode. Multiple sensitivity analyses were performed to assess stability, heterogeneity, and potential horizontal pleiotropy. RESULTS: Twenty-nine hypothyroidism-associated single nucleotide polymorphisms (SNPs) were used as instruments. IVW analysis indicated a significant protective effect of hypothyroidism on glioblastoma (GBM) risk (odds ratio, OR = 0.759; 95% confidence interval, CI: 0.606-0.949; p = 0.016). Consistent estimates were obtained via MR-Egger (OR = 0.565, p = 0.032), weighted median (OR = 0.674, p = 0.017), and weighted mode (OR = 0.581, p = 0.02). Simple mode was non-significant but directionally consistent. Sensitivity analyses showed no heterogeneity or horizontal pleiotropy. CONCLUSION: Employing Mendelian randomization, this investigation provides preliminary genetic evidence suggesting a potential protective association between hypothyroidism and glioblastoma risk. However, the limited case sample (N = 406) and the hypothesis-generating nature of Mendelian randomization (MR) warrant cautious interpretation and replication in larger cohorts....
Citation
Zhou L, Yin C, Zhao W, Kong W, Wang X, Cui G, Wang Y. Hypothyroidism and glioblastoma risk: a two-sample Mendelian randomization study. Neuro Endocrinol Lett. 2026 Mar; 47(1): 29-36