Exploring Novel Biomarkers for Rosacea Through Cohort Study and Mendelian Randomisation

IF 3.1 3区医学 Q1 DERMATOLOGY

Experimental Dermatology Pub Date : 2025-09-01 DOI:10.1111/exd.70161

Rui Mao, Fan Wang, Tongtong Zhang, Ji Li

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Abstract

The current therapeutic landscape for rosacea is notably deficient in targeted medications, underscoring an urgent need for the identification of novel biomarkers. Utilising a longitudinal cohort of 54 306 individuals from the UK Biobank (UKB), we conducted a comprehensive assessment of the associations between 2923 serum proteins and the risk for rosacea. Our cohort analysis identified 18 proteins significantly associated with rosacea risk. Next, we complemented the two-sample Mendelian randomisation (TSMR) and Mendelian randomisation (SMR) analysis based on pooled data to identify genetic links between protein targets and rosacea. TSMR analysis refined this list to nine proteins demonstrating significant causal relationships with at least one form of rosacea. Further refinement through SMR and differential expression analysis reduced this to five key proteins, including four (ABHD14B, CHMP6, DBNL and MCFD2) that inhibit rosacea onset and one (MSR1) that promotes it. The differential expression of these five biomarkers was validated by multiple omics datasets as well as in vitro experiments. We calculated the protein score based on the expression levels of these proteins, noting that participants with higher scores demonstrated an increased incidence of rosacea. The integrative examination of proteomic and genetic data from a European adult cohort provides robust causal evidence for several proteins as promising new biomarkers for the development of rosacea treatments.

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通过队列研究和孟德尔随机化探索新的红斑痤疮生物标志物

目前酒渣鼻的治疗前景明显缺乏靶向药物，强调迫切需要鉴定新的生物标志物。利用来自英国生物银行（UKB）的54 306名个体的纵向队列，我们对2923种血清蛋白与酒渣鼻风险之间的关系进行了全面评估。我们的队列分析确定了18种与酒渣鼻风险显著相关的蛋白质。接下来，我们补充了基于汇总数据的双样本孟德尔随机化（TSMR）和孟德尔随机化（SMR）分析，以确定蛋白质靶点与酒渣鼻之间的遗传联系。TSMR分析将这一列表细化为九种蛋白质，表明与至少一种形式的酒渣鼻有显著的因果关系。通过SMR和差异表达分析进一步细化，将其减少到5个关键蛋白，包括4个（ABHD14B、CHMP6、DBNL和MCFD2）抑制酒渣鼻发病，1个（MSR1）促进酒渣鼻发病。通过多个组学数据集和体外实验验证了这五种生物标志物的差异表达。我们根据这些蛋白质的表达水平计算蛋白质得分，注意到得分较高的参与者表明酒渣鼻的发病率增加。来自欧洲成人队列的蛋白质组学和遗传学数据的综合检查为几种蛋白质作为有希望的新生物标志物提供了强有力的因果证据，用于开发酒渣鼻治疗。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Experimental Dermatology 医学-皮肤病学

CiteScore

6.70

自引率

5.60%

发文量

201

审稿时长

2 months

期刊介绍： Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.