Genetic Association Between Hypothyroidism and the Risk of Trigeminal Neuralgia: A Two-Sample Mendelian Randomisation Study.

Objective: To use Mendelian randomisation (MR) for determining the causal relationship between hypothyroidism and trigeminal neuralgia (TN).

Study design: Analytical study.                                                                                                             Place and Duration of the Study: Department of Neurosurgery, Yantai Yuhuangding Hospital, Yantai, Shangdong, China, from January to April 2024.

Methodology: Fifty hypothyroidism-related single nucleotide polymorphisms (SNPs) were retrieved as instrumental variables (IVs) from the genome-wide association studies (GWAS). MR analysis was conducted using summary statistics from GWAS in the European individuals. The inverse variance weighted (IVW) method was the main tool for finding causality. Other MR methods supported the IVW results and helped confirm the causality results. The additional methods strengthened the findings. Finally, multiple sensitivity studies were conducted to evaluate stability, heterogeneity, and horizontal pleiotropy.

Results: The IVW method showed a strong link between hypothyroidism and TN (p = 0.009). MR-Egger regression revealed that directional pleiotropy was unlikely to bias the results (p = 0.351). Evidence of a causal relationship between hypothyroidism and TN was also found using the weighted median (p = 0.008) and weighted mode (p = 0.016) approaches. Although the simple model showed a null causal effect, it showed a trend similar to that of several other methods.

Conclusion: The results of the MR study corroborate the possibility that hypothyroidism and the risk of TN are directly related.

Key words: Hypothyroidism, Trigeminal neuralgia, Mendelian randomisation, Single nucleotide polymorphisms, Genetics.