Evidence map›Paper›PMID 42434318›Full record

ArticleGlobal medical genetics2026

Integrating multi-omics and mendelian randomization identifies therapeutic targets for Lichen Sclerosus: A druggable genome-wide study.

Shuai Wang, Pengfei Wang, Haiping Li, Xinyi Guan, Shuling Ji, Xian Zhang, Yuanhong Chen, Nan Li, Hu Li, Lujiadai Xue and 1 more

Abstract read
In one paragraph

Article in Global medical genetics, 2026. 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

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Shuai WangDepartment of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Pengfei WangDepartment of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Haiping LiDepartment of Gynecology, Guangdong Women and Children Hospital, Guangzhou 511442, China.
Xinyi GuanDepartment of Gynecology, Guangdong Women and Children Hospital, Guangzhou 511442, China.
Shuling JiDepartment of Gynecology, Guangdong Women and Children Hospital, Guangzhou 511442, China.
Xian ZhangDepartment of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Yuanhong ChenDepartment of Gynecology, Dongguan Eastern Central Hospital, Dongguan 523000, China.
Nan LiDepartment of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Hu LiDepartment of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Lujiadai XueDepartment of Gynecology, The First Affiliated Hospital of Jinan University, Guangzhou 510632, China.
Chunmei ZhaoDepartment of Gynecology, Guangdong Women and Children Hospital, Guangzhou 511442, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Lichen sclerosus (LS) is a chronic inflammatory skin disease characterized by limited treatment options and an unclear pathogenesis. This study aimed to identify potential therapeutic targets for LS by integrating druggable genome (DG) data with multi-omics and Mendelian randomization (MR). Methods: Blood expression quantitative trait loci (eQTLs) were obtained from the eQTLGen consortium, and protein quantitative trait loci (pQTLs) were sourced from the UK Biobank Pharma Proteomics Project (UKB-PPP) and the Decode cohorts. Outcome data for LS were derived from the FinnGen R12 database. We performed two-sample MR analyses to estimate the causal effects of druggable genes on LS, followed by sensitivity analyses, Steiger directionality tests, and multi-omics integration. For multi-omics integration, we cross-referenced eQTL- and pQTL-derived causal genes to identify overlapping genes supported by both transcriptomic and proteomic evidence. Functional concordance was further assessed by comparing effect directions and magnitudes between the two molecular layers. Potential drugs were predicted using the DGIdb database, and molecular docking was performed using CB-Dock2. Results: After rigorous screening and Holm-Bonferroni correction, we identified 50 druggable genes (eQTL-derived) and 35 druggable proteins (pQTL-derived) with causal effects on LS. Integrative multi-omics analysis revealed integrin subunit beta 2 (ITGB2) and poly(ADP-ribose) polymerase 1 (PARP1) as the most robust therapeutic targets. Phenome-wide association study (PheWAS) analysis indicated no significant pleiotropic effects for these genes. Protein-protein interaction and pathway enrichment analyses showed that these genes are involved in integrin-mediated cell adhesion and ADP-ribosylation processes. The DGIdb database predicted 24 potential drugs targeting ITGB2 and PARP1, and molecular docking confirmed strong binding affinities (Vina score < -5). Conclusion: This integrative MR study identifies ITGB2 and PARP1 as promising therapeutic targets for LS, providing a foundation for future drug development and personalized treatment strategies.

Indexed as

druggable genomeITGB2Lichen sclerosusMendelian randomizationmulti-omics integrationPARP1therapeutic targets

Identifiers

PMID42434318
PMCPMC13351453

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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.