Evidence map›Paper›PMID 42444156›Full record

ArticleEndocrine, metabolic & immune disorders drug targets2026

Genetically Predicted 12,13-DiHOME Mediates the Association between TNF-Related Apoptosis-Inducing Ligand and Immune Thrombocytopenia.

Chendong Jiang, Yiwen Chen, Jun Liang, Yang Feng, Zhanyan Gao, Zhan Sun, Jie Wang

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Article in Endocrine, metabolic & immune disorders drug targets, 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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4 · The record

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5 · Who and what money

Authors and funding

7 authors.

Chendong JiangDepartment of Laboratory Medicine, the Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.ORCID 0009-0000-7418-9334
Yiwen ChenDepartment of Dermatology, Huashan Hospital, Fudan University, China.ORCID 0009-0005-7550-147X
Jun LiangDepartment of Dermatology, Huashan Hospital, Fudan University, China.ORCID 0000-0001-5318-4323
Yang FengDepartment of Dermatology, Huashan Hospital, Fudan University, China.ORCID 0000-0003-4861-0759
Zhanyan GaoDepartment of Dermatology, Huashan Hospital, Fudan University, China.ORCID 0009-0008-7478-561X
Zhan SunDepartment of Dermatology, Huashan Hospital, Fudan University, China.ORCID 0009-0006-8894-6643
Jie WangDepartment of Dermatology, Huashan Hospital, Fudan University, China.ORCID 0000-0002-8807-6565

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionThe role of Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand (TRAIL) has been highlighted in autoimmune and metabolic disorders. However, there is still an inadequate explanation of its causal relationship with primary immune thrombocytopenia (ITP). This study employed Mendelian Randomization (MR) to identify the potential causal associations among TRAIL, plasma metabolites, and ITP.

methodsThis study was conducted focusing on analyzing data from a Genome-Wide Association Study (GWAS) comprising inflammatory proteins, plasma metabolites, and the FinnGen consortium. The Inverse Variance Weighted (IVW) method was adopted to derive the causal estimates primarily. Sensitivity analyses included Cochran's Q test for heterogeneity, MR-Egger regression for horizontal pleiotropy, leave-one-out analysis, and validation via Bayesian Weighted MR (BWMR). In addition, the identification and quantification of potential mediating metabolites were realized through a two-step MR approach.

resultsGenetically predicted higher TRAIL levels were associated with a reduced risk of ITP (IVW odds ratio [OR] = 0.78, 95% confidence interval [CI]: 0.65-0.92, p = 0.0042), which was confirmed by BWMR (OR = 0.77, 95% CI: 0.65-0.92, p = 0.0043). Reverse MR analysis revealed no significant causal effect of ITP on TRAIL. Among the 48 plasma metabolites causally associated with TRAIL, only 12,13-dihydroxyoctadecenoic acid (12,13-DiHOME) exhibited a significant association with ITP in BWMR (OR = 0.75, 95% CI: 0.58-0.97, p = 0.0316). Mediation analysis suggested that 12,13-DiHOME might partially mediate the effect of TRAIL on ITP, with an exploratory estimated mediation proportion of 7.55%. DISCUSSION: Mediation analysis revealed that 12,13-DiHOME mediated 7.55% of the TRAIL-related ITP risk reduction. These findings provide preliminary evidence supporting a potential mediating role of 12,13-DiHOME in the protective effect of TRAIL against ITP, suggesting the existence of an immunometabolic pathway linking TRAIL to ITP pathogenesis.

conclusionThis MR study provides genetic evidence of the potentially protective causal effect of TRAIL against ITP, which may be mediated partially by 12,13-DiHOME. Our findings may highlight a novel immunometabolic pathway in ITP pathogenesis, meriting further investigation.

Indexed as

Purpura, Thrombocytopenic, IdiopathicTNF-Related Apoptosis-Inducing LigandGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, human1213-DiHOMEbayesian weighted Mendelian randomizationimmune thrombocytopeniaMendelian randomizationplasma metabolitesTNF-related apoptosis-inducing ligand

Identifiers

PMID42444156
PMCPMC13598743

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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 Socratic graph.