Two-sample Mendelian randomization to study the causal relationship between hyperthyroidism and intervertebral disc degeneration

Abstract

Abstract Objective The primary aim of this study was to meticulously investigate the potential causal relationship between hyperthyroidism and intervertebral disc degeneration(IDD) through the application of a two-sample Mendelian randomization approach. Methods A thorough analysis was conducted, leveraging information on 9,851,867 single nucleotide polymorphisms (SNPs) associated with disc degeneration and 958,783,836 SNPs associated with hyperthyroidism, meticulously collected from pooled gene-wide association study (GWAS) data. Notably, the GWAS pooled data for hyperthyroidism and disc degeneration originated from European populations, with a robust dataset of 484,598 samples for hyperthyroidism and 463,010 samples for disc degeneration. With disc degeneration as the outcome variable and hyperthyroidism as the exposure factor, instrumental variables closely linked to hyperthyroidism were scrupulously identified as single nucleotide polymorphisms. Subsequently, a rigorous two-sample Mendelian randomization analysis was executed, employing three distinct methodologies: inverse variance weighting, MR-Egger regression, and the weighted median method. These methodologies were specifically chosen to comprehensively evaluate the causal relationship between hyperthyroidism and the risk of intervertebral disc degeneration, quantified by odds ratio (OR) values. Results The inclusion of 19 single nucleotide polymorphisms as instrumental variables yielded robust outcomes. MR-Egger regression analysis revealed an absence of horizontal pleiotropy of genes (P = 0.910). Furthermore, the results from the inverse variance weighting method indicated that an escalated prevalence of hyperthyroidism was notably associated with an increased risk of intervertebral disc degeneration. Specifically, a significant 10% rise in the risk of intervertebral disc degeneration was observed for each standard deviation increase in log-transformed hyperthyroidism (OR = 1.1, 95% CI: 1.03 to 1.18). Conclusion In summation, these comprehensive findings strongly suggest the existence of a potential causal association between hyperthyroidism and the progressive development of intervertebral disc degeneration. This nuanced exploration contributes significantly to our understanding of the interplay between hyperthyroidism and disc degeneration and holds implications for future research and clinical considerations.