No Genetic Causal Association between Iron Status and Intervertebral Disc Degeneration: A Two-Sample Mendelian Randomization Study

Many clinical and basic studies have shown an association between iron status and intervertebral disc degeneration (IVDD). However, their causal relationship is still unclear. The aim of this study was to explore the genetic causality between iron status and IVDD using Mendelian randomization. Random effects inverse variance weighted (IVW) meta-analysis was the primary method of analysis, with MR‒Egger, weighted median, simple modal, and weighted modal methods as secondary methods. Subsequently, we used IVW, MR‒Egger, MR-PRESSO, and leave-one-out analyses to test for heterogeneity and horizontal pleiotropy. Finally, we used the maximum likelihood, penalized weighted median and IVW (fixed effects) methods to further verify the reliability of the results. Random-effects IVW and IVW meta-analyses revealed that transferrin, total iron binding capacity (TIBC), ferritin, iron, and transferrin saturation (TSAT) were not genetically causally related to IVDD, and removal of outliers detected by MR-PRESSO resulted in broad consistency. Our study revealed that there is no genetic causal relationship between iron status and IVDD, but it cannot be excluded that there is a correlation between the two at a level other than genetics.