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. 2025 Feb 1;15(1):4019.
doi: 10.1038/s41598-025-86447-4.

Copper and iron as unique trace elements linked to fibromyalgia risk

Wenxing Zeng  1   2 , Minhua Hu  3 , Luyao Ma  1   2 , Feng Huang  1   2 , Ziwei Jiang  4   5
Affiliations

Copper and iron as unique trace elements linked to fibromyalgia risk

Wenxing Zeng et al. Sci Rep. .

Abstract

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.

Keywords: Causality; Copper; Fibromyalgia; Iron; Mendelian randomization; Multivariate analysis; Trace elements.

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Conflict of interest statement

Declarations. Competing interests: The authors declare that this study was conducted without any commercial or financial relationship, which could be interpreted as a potential conflict of interest. Ethical approval: was not required for this study involving human data, in accordance with local legislation and institutional requirements. Similarly, written informed consent to participate was not necessary from the participants or their legal guardians/next of kin, as per national legislation and institutional guidelines. These decisions were based on the fact that the study used de-identified, publicly available data sets where participants’ privacy and confidentiality are inherently protected. institutional requirements.

Figures

Fig. 1
Fig. 1
Mendelian randomisation (MR) design flowchart.
Fig. 2
Fig. 2
Results of 15 trace elements with FM MR analysis (IVW & WME).
Fig. 3
Fig. 3
Positive results in 15 trace elements.
Fig. 4
Fig. 4
Results of five MR analyses between elemental selenium and FM.
Fig. 5
Fig. 5
Results of MR analyses of copper versus FM, including (A) scatter plots, (B) forest plots, (C) leave-one-out method, (D) funnel plots.
Fig. 6
Fig. 6
Results of MR analyses of iron versus FM, including (A) scatter plots, (B) forest plots, (C) leave-one-out method, (D) funnel plots.
Fig. 7
Fig. 7
Multivariate MR analyses were performed to correct for confounding effects of selenium on the effects of Cu and Fe with FM.
See this image and copyright information in PMC

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