Sleep factors and risk of thyroid cancer, nodules and dysfunction: Mendelian randomization study

Background: The interplay between sleep physiology and endocrine regulation has been well-established, with the thyroid gland, as a key endocrine organ, demonstrating a physiologically plausible. Previous studies have indicated a potential correlation between sleep factors and thyroid diseases, yet causality remains uncertain. Given the complex interplay of confounders associated with sleep disorders and lifestyle factors, we employed a two-sample Mendelian randomization (MR) approach to minimize confounding bias and rigorously investigate the causal relationship. Methods: The specific information on thyroid diseases-including thyroid cancer, thyroid nodules (TNs), and thyroid dysfunction-was obtained from the FinnGen Biobank using the International Classification of Diseases, 10th Revision (ICD-10). Information on sleep factors such as insomnia symptoms, chronotype, and sleep duration were sourced from genome-wide association studies (GWAS) conducted within the UK Biobank, which provides validated GWAS data through self-report assessment. We employed stringent single nucleotide polymorphisms (SNPs) selection criteria as instrumental variables (IVs) for analyzing sleep factors' causal impact on thyroid diseases. Statistical methods including inverse variance weighted (IVW), weighted median (WM), MR-Egger, and MR-PRESSO were utilized to determine causality, supplemented by F-statistics and sensitivity analyses to ensure robustness and detect biases. Results: The analysis supported that a morning chronotype is protective against thyroid cancer, with results showing a significantly reduced risk [IVW: odds ratio (OR) =0.632, 95% confidence interval (CI): 0.426- 0.937, P=0.02]. Conversely, insomnia symptoms were identified as a potential risk factor for developing TNs (IVW: OR =1.973, 95% CI: 1.152-3.377, P=0.01). Sensitivity analyses, including Cochran's Q test, MREgger intercept, and MR-PRESSO, showed no significant heterogeneity, horizontal pleiotropy, or outliers (all P values >0.05). However, no significant causal links were found between genetic predispositions to sleep factors and thyroid dysfunction. Conclusions: These findings suggest that therapeutic management of sleep disorders could potentially reduce the risk of developing thyroid diseases, underscoring the importance of routine thyroid monitoring in individuals experiencing sleep disturbances.