Evidence map›Paper›PMID 39918628›Full record

ArticleArchives of dermatological research2025

Identifying potential drug targets for seborrheic keratosis through druggable genome-wide Mendelian randomization and colocalization analysis.

Zhipeng Lin, Hongyong Sun, Zeng Zhao, Aoxue Wang

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Article in Archives of dermatological research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

4 authors.

Zhipeng LinDepartment of Dermatology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, China.ORCID http://orcid.org/0000-0001-9811-5436
Hongyong SunDepartment of Dermatology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, China.
Zeng ZhaoDepartment of Dermatology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, China.
Aoxue WangDepartment of Dermatology, The Second Hospital of Dalian Medical University, No. 467 Zhongshan Road, Shahekou District, Dalian, 116023, China. wangaxdl@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Seborrheic keratosis (SK) is the most prevalent benign epidermal tumor in adults, characterized by complex pathogenesis and diverse clinical subtypes. This study systematically evaluated the genetic susceptibility and identified novel therapeutic targets for SK. We applied two-sample Mendelian randomization (MR) using cis-eQTL data for druggable genes in blood and SK genome-wide association study (GWAS) data to identify causal genes. Sensitivity and colocalization analyses were performed to assess MR reliability and estimate the likelihood of shared causal variants between cis-eQTLs of druggable genes and SK. For additional validation, we conducted enrichment analysis, phenome-wide association analysis, and candidate drug prediction to further interpret our findings. The expression levels of 18 druggable genes were significantly associated with SK susceptibility (adjusted p-value [FDR] < 0.05), of which 8 were identified as risk factors for SK, while 10 significantly reduced SK predisposition. The susceptibility of SK was likely linked to a shared causal variant with two significant druggable genes, CASP8 (OR = 0.725, 95%CI: 0.622-0.844, PPH4 = 0.907) and TSSK6 (OR = 0.478, 95%CI: 0.327-0.696, PPH4 = 0.970). Functional analyses revealed CASP8 and TSSK6 may influence SK onset and progression through mechanisms cell differentiation and programmed apoptosis regulation. CASP8 and TSSK6 stand out as the most promising potential drug targets for reducing the susceptibility of SK. Our findings identify potential drug targets and provide valuable insights for future SK drug development.

Indexed as

Keratosis, SeborrheicCaspase 8Genetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideQuantitative Trait LociRisk FactorsCASP8 protein, humanCaspase 8CASP8Druggable genesMendelian randomizationSeborrheic keratosisTargeted drugsTSSK6

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.