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. 2025 May;24(5):e70248.
doi: 10.1111/jocd.70248.

Evaluating the Causal Relationship Between Human Blood Metabolites and the Susceptibility to Alopecia Areata

Xiaoli Lei  1 , Yi Qu  1 , Jiaxi Huang  2
Affiliations

Evaluating the Causal Relationship Between Human Blood Metabolites and the Susceptibility to Alopecia Areata

Xiaoli Lei et al. J Cosmet Dermatol. 2025 May.

Abstract

Background: Alopecia areata, a common autoimmune disease, is not fully understood in terms of its cause. However, research suggests that an imbalance in specific blood metabolites may trigger immune system dysfunction, leading to an attack on hair follicles and ultimately resulting in alopecia areata.

Methods: Two-sample MR analysis was conducted to investigate the causal relationship between plasma metabolites and alopecia areata using various methods. Heterogeneity and pleiotropy were assessed, robustness of findings evaluated, and reverse MR performed for effect analysis.

Results: The MR analysis found a positive causal relationship between alpha-ketoglutarate, propionylcarnitine (c3) and other metabolites with alopecia areata risk. Conversely, xylose 3-(3-hydroxyphenyl)propionate, glycochenodeoxycholate glucuronide (1) along with other metabolites, showed a protective effect against alopecia areata development. Both BWMR and MR-PRESSO confirmed the accuracy of the above results. Reverse MR revealed no reverse causality between plasma metabolites and AA. The robustness of the results was confirmed using the leave-one-out method, which demonstrated no influential instrumental variables affecting the outcomes while accounting for heterogeneity and eliminating horizontal gene pleiotropy effects on estimating causal effects.

Conclusion: This study establishes a causal relationship between plasma metabolism and alopecia areata, enhancing our understanding of its underlying mechanisms. These findings also provide valuable references for future screening and prevention strategies.

Keywords: 1400 blood metabolites; Mendelian randomization; alopecia areata; causality.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
A two‐way MR design.
FIGURE 2
FIGURE 2
Positive causal relationship between 1400 plasma metabolites and AA based on IVW and BWMR.
FIGURE 3
FIGURE 3
Negative causal relationship between 1400 plasma metabolites and AA based on IVW and BWMR.
See this image and copyright information in PMC

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