Evidence map›Paper›PMID 40495522›Full record

ArticleBrain and behavior2025

Proteome-Wide and Immune Cell Phenotype Mendelian Randomization Highlights Immune Involvement in Genetic Generalized Epilepsy.

Jianxiong Gui, Hongyuan Chu, Junjiao Zhang, Xiao Li, Wenwei Liu, Renqiuguo Li, Fan Zhang, Meiyu Dong, Kai Gao, Huaxia Luo and 1 more

Abstract read
In one paragraph

Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
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

11 authors.

Jianxiong GuiChildren's Medical Center, Peking University First Hospital, Beijing, China.
Hongyuan ChuChildren's Medical Center, Peking University First Hospital, Beijing, China.
Junjiao ZhangChildren's Medical Center, Peking University First Hospital, Beijing, China.
Xiao LiChildren's Medical Center, Peking University First Hospital, Beijing, China.
Wenwei LiuChildren's Medical Center, Peking University First Hospital, Beijing, China.
Renqiuguo LiChildren's Medical Center, Peking University First Hospital, Beijing, China.
Fan ZhangChildren's Medical Center, Peking University First Hospital, Beijing, China.
Meiyu DongChildren's Medical Center, Peking University First Hospital, Beijing, China.
Kai GaoChildren's Medical Center, Peking University First Hospital, Beijing, China.
Huaxia LuoChildren's Medical Center, Peking University First Hospital, Beijing, China.
Yuwu JiangChildren's Medical Center, Peking University First Hospital, Beijing, China.ORCID https://orcid.org/0009-0006-5234-5619

Funding

Beijing  Municipal Natural Science Foundation 7254426China Postdoctoral Science Foundation 2024M760146Key Project of Clinical Medicine Research of National Clinical Research Center for Child Health and Disorders, Children's Hospital of Chongqing Medical University NCRCCHD-2021-KP-02
6 · The paper itself

Abstract

introductionGenetic generalized epilepsy (GGE) involves polygenic inheritance, with emerging evidence implicating immune mechanisms in seizure pathogenesis. Unlike previous studies focusing on inflammation following seizures, we employed an integrative multi-omics approach to identify precipitating immune factors in GGE development.

methodsSummary data on plasma protein levels were extracted from two large protein quantitative trait loci (pQTLs) studies, measuring 4907 and 2923 plasma proteins in 35,559 and 54,219 individuals, respectively. Immune cell trait data were derived from a genome-wide association study (GWAS) involving 3757 individuals. GGE data, comprising 7407 cases and 52,538 controls, were sourced from a GWAS meta-analysis by the International League Against Epilepsy (ILAE). Mendelian randomization (MR) analysis identified associations between plasma proteins, immune cell phenotypes, and GGE. Colocalization analysis assessed whether plasma proteins and GGE share a common causal variant. Transcriptome-wide association studies (TWAS) from GTEx v8 brain tissue and whole blood were conducted for validation. Drug target prediction and molecular docking identified potential therapeutic interventions.

resultsWe identified 62 potential susceptibility proteins by integrating GWAS data for GGE and its subsyndromes with plasma proteomics data. Of these, eight proteins showed strong evidence of colocalization, primarily within immune-related pathways. The absolute count of TD CD4

conclusionThese findings revealed causal associations between plasma proteins and GGE, prioritized immune-related biological pathways, and proposed potential therapeutic hypotheses targeting immunomodulatory mechanisms.

Indexed as

Epilepsy, GeneralizedBlood ProteinsGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisMultifactorial InheritancePhenotypeProteomeQuantitative Trait LociBlood ProteinsProteomegenetic generalized epilepsyMendelian randomizationplasma proteins

Identifiers

PMID40495522
PMCPMC12152256

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.