Causal Relationships Between Plasma Metabolites and Risk of Dermatomyositis.

IF 2.2 4区医学 Q3 DERMATOLOGY

Clinical, Cosmetic and Investigational Dermatology Pub Date : 2025-10-13 eCollection Date: 2025-01-01 DOI:10.2147/CCID.S538895

Wenyi Qin, Jiayu Tian, Yuqin Qiu, Xiaorong Bao, Shuangshuang Yang

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Abstract

Purpose: This exploratory study aimed to investigate the potential causal relationships between plasma metabolites and dermatomyositis using Mendelian randomization (MR), with the goal of generating hypotheses for future research.

Patients and methods: We screened well-established metabolite GWAS databases and a comprehensive dermatomyositis patient database, starting with 1,400 metabolites. Suitable instrumental variables (IVs) were selected based on genome-wide significance, LD independence (r² < 0.01), and F-statistics > 10 to minimize weak instrument bias and pleiotropy. These IVs were then integrated with dermatomyositis patient data for MR analysis, employing techniques such as inverse-variance weighting (IVW), MR-Egger regression, and weighted median approaches. Sensitivity analyses were conducted to ensure result robustness, and findings were visualized using forest plots, scatter plots, and funnel plots.

Results: The IVW method revealed 53 metabolites and metabolic ratios significantly associated with dermatomyositis. Specifically, 20 metabolites and 8 metabolic ratios were linked to a decreased risk, while 17 metabolites and 8 ratios indicated increased risk. However, none of these associations remained statistically significant after false discovery rate (FDR) correction. Notable heterogeneity was observed in Lactosyl-N-palmitoyl-sphingosine levels, and pleiotropy was evident with 3-carboxy-4-methyl-5-pentyl-2-furanpropionate (3-CMPFP). Robustness was confirmed through MR-PRESSO and leave-one-out analyses.

Conclusion: This study conducted the first exploratory Mendelian randomization analysis to investigate potential causal links between plasma metabolites and dermatomyositis. Although no statistically significant causal relationships were identified after multiple testing correction, this study provides preliminary evidence and valuable hypotheses for further research into metabolic pathways underlying dermatomyositis.

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血浆代谢物与皮肌炎风险的因果关系。

目的：本探索性研究旨在利用孟德尔随机化（Mendelian randomization， MR）研究血浆代谢物与皮肌炎之间的潜在因果关系，为未来的研究提出假设。患者和方法：我们筛选了完善的代谢物GWAS数据库和一个全面的皮肌炎患者数据库，从1400个代谢物开始。根据全基因组显著性、LD独立性（r²< 0.01）和f -统计量bbb10选择合适的工具变量，以最大限度地减少弱工具偏倚和多效性。然后将这些IVs与皮肌炎患者数据相结合进行MR分析，采用反方差加权（IVW）、MR- egger回归和加权中位数法等技术。进行敏感性分析以确保结果稳健性，并使用森林图、散点图和漏斗图将结果可视化。结果：IVW方法显示53种代谢产物和代谢比率与皮肌炎有显著相关性。具体来说，20种代谢物和8种代谢比率与风险降低有关，而17种代谢物和8种代谢比率表明风险增加。然而，在错误发现率（FDR）校正后，这些关联在统计上都不显著。乳酰- n -棕榈酰-鞘氨醇水平存在显著异质性，3-羧基-4-甲基-5-戊基-2-呋喃丙酸（3-CMPFP）呈明显的多效性。鲁棒性通过MR-PRESSO和留一分析得到证实。结论：本研究首次进行了探索性孟德尔随机化分析，以调查血浆代谢物与皮肌炎之间的潜在因果关系。虽然经过多次检验校正后没有发现统计学上显著的因果关系，但本研究为进一步研究皮肌炎的代谢途径提供了初步证据和有价值的假设。

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来源期刊

Clinical, Cosmetic and Investigational Dermatology Medicine-Dermatology

CiteScore

2.80

自引率

4.30%

发文量

353

审稿时长

16 weeks

期刊介绍： Clinical, Cosmetic and Investigational Dermatology is an international, peer-reviewed, open access journal that focuses on the latest clinical and experimental research in all aspects of skin disease and cosmetic interventions. Normal and pathological processes in skin development and aging, their modification and treatment, as well as basic research into histology of dermal and dermal structures that provide clinical insights and potential treatment options are key topics for the journal. Patient satisfaction, preference, quality of life, compliance, persistence and their role in developing new management options to optimize outcomes for target conditions constitute major areas of interest. The journal is characterized by the rapid reporting of clinical studies, reviews and original research in skin research and skin care. All areas of dermatology will be covered; contributions will be welcomed from all clinicians and basic science researchers globally.