The Impact of Immune Cells, Metabolites, Inflammatory Factors, and Circulating Proteins on Atopic Dermatitis: Insights from a Mendelian Randomization Study.

IF 1.9 4区医学 Q3 DERMATOLOGY Clinical, Cosmetic and Investigational Dermatology Pub Date : 2024-12-21 eCollection Date: 2024-01-01 DOI:10.2147/CCID.S495217

Dongqi Zhou, Gaofeng Gan, Shiwei Song, Cangyan Zi, Yichen Bao, Wenfeng Hao, Qiu Chen

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Abstract

Background: The onset of atopic dermatitis (AD) is complex, and its specific pathological mechanisms have not yet been fully elucidated.

Methods: Using circulating multi-omics as the exposure factors and AD as the outcome, we conducted univariable MR analysis. The circulating multi-omics data included immunomics (731 immune cell types), proteomics (4907 plasma proteins), metabolomics (1400 metabolites and 486 additional metabolites), and 91 inflammatory factors. MR analysis was conducted using IVW, WM, Simple Mode, Weighted Mode, and MR-Egger methods, with IVW as the primary analysis tool. To address horizontal pleiotropy, we utilized MR-Egger intercept tests and MR-PRESSO for correction, alongside the Cochrane Q statistic for heterogeneity assessment. Sensitivity analysis was performed using a leave-one-out strategy. To control for false positives due to multiple testing, we set a standard of a 5% false discovery rate. Additionally, we conducted F-statistics on the included SNPs to eliminate the impact of weak instrumental variables.

Results: IL-18R1 on AD (OR = 1.12, 95% CI: 1.08-1.17, P _FDR < 0.01). Mannonate levels on AD (OR = 0.88, 95% CI: 0.83-0.94, P _FDR = 0.03). Retinol (Vitamin A) to linoleoyl-arachidonoyl-glycerol (18:2 to 20:4) on AD (OR = 1.12, 95% CI: 1.06-1.18, PFDR = 0.03). HVEM on CM CD4+ cells on AD (OR = 0.81, 95% CI: 0.75-0.88, P _FDR < 0.01). CR2 on AD (OR = 0.81, 95% CI: 0.72-0.90, P _FDR = 0.04). MANSC1 on AD (OR = 0.87, 95% CI: 0.81-0.93, P _FDR = 0.04). IL18R1 (4097 inflammatory markers) on AD (OR = 1.11, 95% CI: 1.06-1.17, P _FDR = 0.01). HNRNPAB on AD (OR = 1.44, 95% CI: 1.23-1.70, P _FDR < 0.01).

Conclusion: This study further explored the correlations between multi-omics data and AD. We identified seven previously unreported circulating substances with causal relationships to AD, filling a current theoretical gap.

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免疫细胞、代谢物、炎症因子和循环蛋白对特应性皮炎的影响：来自孟德尔随机研究的见解。

背景：特应性皮炎（AD）发病复杂，其具体病理机制尚未完全阐明。方法：以循环多组学为暴露因素，以AD为结局，进行单变量MR分析。循环多组学数据包括免疫组学（731种免疫细胞类型）、蛋白质组学（4907种血浆蛋白）、代谢组学（1400种代谢物和486种额外代谢物）和91种炎症因子。以IVW为主要分析工具，采用IVW、WM、Simple Mode、Weighted Mode和MR- egger方法进行MR分析。为了解决水平多效性问题，我们使用MR-Egger截距检验和MR-PRESSO进行校正，并使用Cochrane Q统计量进行异质性评估。采用留一策略进行敏感性分析。为了控制由于多次测试而产生的误报，我们设置了5%的错误发现率标准。此外，我们对纳入的snp进行f统计，以消除弱工具变量的影响。结果：IL-18R1对AD的影响（OR = 1.12, 95% CI: 1.08 ~ 1.17, P FDR < 0.01）。甘露聚糖水平对AD的影响（OR = 0.88, 95% CI: 0.83-0.94, P FDR = 0.03）。视黄醇（维生素A）与亚油酰-花生四烯醇-甘油（18:2至20:4）在AD （OR = 1.12, 95% CI: 1.06-1.18, PFDR = 0.03）。HVEM对AD患者CM CD4+细胞的影响（OR = 0.81, 95% CI: 0.75 ~ 0.88, P FDR < 0.01）。CR2对AD的影响（OR = 0.81, 95% CI: 0.72-0.90, P FDR = 0.04）。MANSC1对AD的影响（OR = 0.87, 95% CI: 0.81-0.93, P FDR = 0.04）。IL18R1（4097炎症标志物）对AD的影响（OR = 1.11, 95% CI: 1.06-1.17, P FDR = 0.01）。HNRNPAB对AD的影响（OR = 1.44, 95% CI: 1.23 ~ 1.70, P FDR < 0.01）。结论：本研究进一步探讨了多组学数据与AD的相关性。我们确定了7种以前未报道的与AD有因果关系的循环物质，填补了目前的理论空白。

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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.