Evidence map›Paper›PMID 41398839›Full record

SynthesisMedicine2025

Identification of therapeutic targets for insomnia through genetic and plasma proteomic approaches.

Xueying Wang, Jun Lu, Fuhong Lin, Guoli Li, Weili Zhao

Abstract readMeta-Analysis
In one paragraph

Synthesis in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

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.

Xueying WangDepartment of Neurology, Affiliated Hospital of Chifeng University, Chifeng, Inner Mongolia, China.ORCID 0009-0006-4835-423
Jun Lu
Fuhong Lin
Guoli Li
Weili Zhao

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Insomnia is a prevalent sleep disorder, and for which effective therapeutic targets remain lacking. In this study, we conducted a GWAS meta-analysis on 3 datasets: ukb-b-3957, FinnGen R10, and ebi-a-GCST004695, using METAL. Building on this, we further investigated the causality of plasma proteins using a protein Mendelian randomization (MR) approach. The MR analysis utilized protein datasets from deCODE and UKB, incorporating co-localization. Reverse MR was employed to examine the potential presence of reverse causality. MAGMA was employed to investigate key proteins associated with insomnia, along with tissue enrichment analysis. The insomnia GWAS meta-analysis revealed that 250 genes exhibited statistically significant signals after FDR correction (P < .05). A total of 81 risk loci were identified (P < 5e-8), and the risk genes were predominantly enriched in tissues such as the cerebellum, cerebellar hemisphere, and prefrontal cortex. Our PW-MR analysis identified 36 proteins with replicated causal associations with insomnia. After excluding one protein (HEXIM1) due to evidence of reverse causality, we established a final list of 35 high-confidence candidate proteins. Further colocalization analysis supported a shared causal variant for several candidates, including DNPH1 and PTK7. This study identifies a robust list of plasma proteins with genetically-predicted causal links to insomnia risk. These findings offer a valuable resource for subsequent functional validation studies aimed at elucidating the molecular mechanisms underlying the disorder.

Indexed as

Blood ProteinsProteomicsSleep Initiation and Maintenance DisordersGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMendelian Randomization AnalysisBlood ProteinsGWAS metainsomniaMAGMAMendelian randomizationproteomics

Identifiers

PMID41398839
PMCPMC12708154

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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.