Plain language summary
Hyperthyroidism is a condition characterised by excessive production of thyroid hormones, which can lead to various metabolic disturbances and health complications. Understanding the causal relationships between hyperthyroidism and various biomarkers is crucial for identifying potential therapeutic targets and improving patient outcomes. The primary aim of this study was to validate the causal relationships between specific biomarkers and the risk of developing hyperthyroidism using a robust statistical framework. This research is a bidirectional Mendelian randomisation (MR) study combined with a meta-analysis, analysing genetic variants associated with both the biomarkers and hyperthyroidism across multiple datasets. Results showed a positive correlation between total bilirubin levels and hyperthyroidism: - that only one group of blood biomarkers (total bilirubin levels) is causally associated with hyperthyroidism. - the MR analysis showed that the blood biomarker total bilirubin levels only unidirectionally influences hyperthyroidism, and there is no evidence of hyperthyroidism affecting total bilirubin levels in return. Authors concluded that total (urine) bilirubin is a risk factor for hyperthyroidism and may accelerate the onset and progression of the disease. Thus, through early detection of total bilirubin levels, clinicians can identify high-risk groups and intervene early, thereby significantly improving outcomes.
Abstract
BACKGROUND Hyperthyroidism is an endocrine disorder with a relatively low global prevalence but significantly higher incidence among females compared to males. The onset age primarily ranges from 30 to 50, although it is not limited to this age group. Challenges in the treatment of hyperthyroidism include individualized treatment plan formulation, management of side effects, and prediction of disease progression, necessitating comprehensive consideration to achieve more effective therapy and management. Mendelian randomization studies can reveal more precise therapeutic targets between blood and urine biomarkers and hyperthyroidism, providing more decadent treatment options for the condition. METHODS The study will build upon the omics Mendelian randomization (MR) framework by conducting MR analysis using 35 blood and urine biomarkers separately for two distinct databases of hyperthyroidism. Subsequently, the results will undergo meta-analysis and multiple corrections to ensure accuracy and reliability. Finally, positive findings will undergo reverse MR validation to verify causal relationships with hyperthyroidism. RESULTS In the British database, the MR analysis of Total bilirubin levels about hyperthyroidism yielded an odds ratio (OR) of 1.097 (95% CI: 0.951-1.265, P = 0.205). Conversely, in the Thyroid Omics Association database, the MR analysis revealed an OR of 1.283 (95% CI: 1.122-1.467, P = 0.0002) for the same relationship. Meta-analysis of the MR analysis results from both databases, following multiple corrections, resulted in an OR of 1.192 (95% CI: 1.081-1.314, P = 0.015). Additionally, the direction of beta values in the MR analysis results from both databases was consistent. CONCLUSION The urine biomarker total bilirubin levels may contribute to an increased risk of hyperthyroidism and accelerate its progression, thus representing a risk factor for the condition.
Methodological quality
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