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. 2025 Jan;24(1):e16763.
doi: 10.1111/jocd.16763.

Unraveling the Causal Relationship Between Blood Metabolites and Acne: A Metabolomic Mendelian Randomization Study

Min Li  1 , Dan Dan Zhan  1 , Li Li Fan  1 , Yu Wang  1 , Xiao Han Hu  1 , Ming Zhang  1 , Zhou Zhou  1
Affiliations

Unraveling the Causal Relationship Between Blood Metabolites and Acne: A Metabolomic Mendelian Randomization Study

Min Li et al. J Cosmet Dermatol. 2025 Jan.

Abstract

Background: Acne is a common skin disorder that may be linked to metabolic dysfunction. However, the causal impact of blood metabolites on acne has not been thoroughly investigated.

Methods: We performed a metabolome-wide Mendelian randomization (MR) analysis on 486 blood metabolites and acne using a genome-wide association dataset. The study included preliminary inverse-variance weighted (IVW) analysis, multivariable MR analysis, linkage disequilibrium score (LDSC) analysis, and colocalization analysis, along with reverse MR to address potential reverse causation.

Results: Our analysis identified 12 metabolites significantly associated with acne. LDSC analysis revealed a genetic correlation between nonanoylcarnitine and acne. Colocalization analysis confirmed shared genetic variants, and metabolic pathway analysis implicated the arginine biosynthesis pathway and the selenocompound metabolism pathway in the development of acne.

Conclusion: This study offers a comprehensive understanding of the causal relationships between plasma metabolites and acne. The findings provide insights into potential biomarkers and therapeutic targets for acne treatment, underscoring the need for further research.

Keywords: Mendelian randomization; acne; blood metabolites; causality; colocalization analysis; metabolic pathways.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Overview of the Mendelian randomization (MR) analysis. Assumption (1) Strong correlation between genetic instruments and targeted exposures; Assumption (2) Independence of genetic variation from confounders related to the outcome; Assumption (3) Genetic instruments influence the outcome solely through the exposure. IVW, inverse‐variance weighted; LD, linkage disequilibrium; LDSC, linkage disequilibrium score; LOO analysis, leave‐one‐out analysis; MR‐PRESSO, MR‐Pleiotropy RESidual sum and outlier; MVMR, multivariable Mendelian randomization; SNPs, single nucleotide polymorphisms; WM, weighted median.
FIGURE 2
FIGURE 2
Heatmap showing potential causal metabolites (IVW: p < 0.05) linked to acne.
FIGURE 3
FIGURE 3
Forest plot illustrating the causal effect of metabolites on acne risk. CI, confidence interval; IVW, inverse‐variance weighted; OR, odds ratio.
FIGURE 4
FIGURE 4
Forest plot presenting results from multivariable MR analysis. IVW, inverse‐variance weighted; OR, odds ratio.
FIGURE 5
FIGURE 5
Colocalization analysis of candidate blood metabolites related to acne. Plots show genetic evidence of colocalization between acne and (A) 1‐stearoylglycerol at chr1:4688033; (B) isobutyrylcarnitine at chr6:160575366; (C) nonanoylcarnitine at chr2:211043102; (D) 7‐Hoca at chr14:59219801. Each point represents a single‐nucleotide polymorphism (SNP), with the chromosomal position on the x‐axis (within 500‐kb regions of the lead SNP) and − log10 (p‐value) on the y‐axis. Variants are color‐coded by their linkage disequilibrium with the lead SNP. Recombination rates are shown as blue lines, and gene locations are marked at the bottom.
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