Copper and iron as unique trace elements linked to fibromyalgia risk

Fibromyalgia (FM) is a prevalent chronic pain condition with a complex and not fully understood etiology. Abnormal metabolism of trace elements is suspected to play a role in the pathogenesis of FM, though the exact relationships have yet to be clarified. This study employed Mendelian randomization (MR) to assess potential causal relationships between 15 major trace elements and the risk of FM, focusing on the specific roles of elements that show significant associations. Genetic instrumental variables (single nucleotide polymorphisms, SNPs), related to these trace elements and FM were extracted from genome-wide association studies (GWAS). Analyses were performed using various methods including inverse-variance weighting (IVW), MR Egger, weighted median, weighted mode, and simple mode. Furthermore, multivariable analysis controlled for selenium as a potential confounder to evaluate the independent associations of copper (Cu) and iron (Fe) with FM risk. Two-sample MR analysis indicated a positive association between Cu and increased risk of FM (IVW: OR = 1.095, 95% CI: 1.015 to 1.181, P = 0.018), and a negative association between Fe and FM risk (IVW: OR = 0.440, 95% CI: 0.233 to 0.834, P = 0.011). These associations remained significant in the multivariable analysis, highlighting the independent effects of Cu and Fe. No significant correlations were observed with other trace elements such as selenium and zinc. This study provides new evidence of the roles of Cu and Fe in the pathophysiology of FM and underscores the importance of considering trace elements in the prevention and treatment strategies for FM. Future research should further validate these findings and explore the specific biological mechanisms through which Cu and Fe influence FM risk.