Evidence map›Paper›PMID 41333034›Full record

ArticleJournal of inflammation research2025

Multi-Omics Mendelian Randomization Identifies Therapeutic Targets for Sjögren's Disease with Clinical and Bayesian Validation.

Jiale He, Kesong Li, Zilin Guo, Xinyao Zhou, Xiaopo Tang

Abstract read
In one paragraph

Article in Journal of inflammation 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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0citing papers 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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No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Jiale HeDepartment of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People's Republic of China.
Kesong LiDepartment of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People's Republic of China.
Zilin GuoDepartment of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People's Republic of China.
Xinyao ZhouDepartment of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People's Republic of China.
Xiaopo TangDepartment of Rheumatology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People's Republic of China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: There are currently no effective pharmacological treatments for Sjögren's disease (SjD). Our study aims to identify potential therapeutic targets for the condition using druggable genome-wide Mendelian randomization (MR). Methods: Druggable genome data were obtained from the Drug-Gene Interaction Database (DGIdb) and the study by Finan et al. We then integrated these druggable genes with blood-derived cis-eQTL, cis-mQTL, and cis-pQTL datasets, each analyzed separately in two-sample MR analyses using SjD GWAS summary statistics as the outcome, applying a genome-wide MR approach focused on druggable targets. Bayesian colocalization was applied to validate shared causal genetic variants. Protein levels of prioritized genes were validated in clinical serum samples from SjD patients and controls using ELISA. Phenome-wide MR (Phe-MR) analysis was conducted across 1359 phenotypes from the UK Biobank to evaluate potential pleiotropic effects and safety profiles of the identified targets, assessed side effects and alternative indications of identified targets. Results: Fourteen druggable genes were identified, with eight (PLAT, SIRPB1, LAIR2, NEU1, SLC22A16, RAD52, PSPH, and CDH23) demonstrating consistent causal relationships with SjD. ELISA validation supported differential protein expression for these targets. Key findings include the protective role of NEU1 and PSPH in systemic immune regulation, the pathogenic impact of PLAT, SIRPB1, BRD2, and LAIR2 on inflammation, and the potential involvement of SLC22A16 and RAD52 in metabolic stress and immune activation. Existing pharmacological compounds targeting these genes, including Aminocaproic acid, Resveratrol, Levocarnitine, Imatinib, and Zinc chloride were identified as potential therapeutic candidates. No significant adverse effects were detected through Phe-MR analysis. Conclusion: Our research indicated PLAT, SIRPB1, LAIR2, NEU1, SLC22A16, RAD52, PSPH, and CDH23 may serve as promising targets for SjD, while the effectiveness of Aminocaproic acid, Resveratrol, Levocarnitine, Imatinib, and Zinc chloride for SjD requires further validation.

Indexed as

Bayesian colocalizationdruggable genomeMendelian randomizationPhe-MR analysisSjögren’s diseasetherapeutic targets

Identifiers

PMID41333034
PMCPMC12667418

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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.