Evidence map›Paper›PMID 37349091›Full record

ArticleJournal of neurology, neurosurgery, and psychiatry2023

Systematic druggable genome-wide Mendelian randomisation identifies therapeutic targets for Alzheimer's disease.

Wei-Ming Su, Xiao-Jing Gu, Meng Dou, Qing-Qing Duan, Zheng Jiang, Kang-Fu Yin, Wei-Chen Cai, Bei Cao, Yi Wang, Yong-Ping Chen

Open access · hybridAbstract read
In one paragraph

Article in Journal of neurology, neurosurgery, and psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
107citing papers in PubMed, 2 pooled it
47.6field-weighted citation impact, top 1% of its field
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

107 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Genetic susceptibility, risk prediction, and druggable targets for oropharyngeal cancer: a UK Biobank study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2026
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  20. Vascular cognitive impairment and dementia: Prevention, treatments, mechanisms and management options for the future.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review

47 more citing papers are in PubMed but not listed here.

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

10 authors at 3 institutions in 1 country.

Wei-Ming Su *Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Xiao-Jing Gu *Department of Mental Health Center, West China Hospital, Sichuan University, Chengdu, China.
Meng DouChengdu Computer Application Institute, Chinese Academy of Sciences, Chengdu, China.
Qing-Qing DuanDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Zheng JiangDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Kang-Fu YinDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Wei-Chen CaiDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Bei CaoDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Yi WangDepartment of Pathophysiology, West China College of Basic medical sciences & Forensic Medicine, Sichuan University, Chengdu, China.
Yong-Ping ChenDepartment of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China Yongping.chen@wchscu.cn.ORCID 0000-0002-5603-4192
Sichuan University · CNChinese Academy of Sciences · CNWest China Medical Center of Sichuan University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) is the leading cause of dementia. Currently, there are no effective disease-modifying treatments for AD. Mendelian randomisation (MR) has been widely used to repurpose licensed drugs and discover novel therapeutic targets. Thus, we aimed to identify novel therapeutic targets for AD and analyse their pathophysiological mechanisms and potential side effects.

methodsA two-sample MR integrating the identified druggable genes was performed to estimate the causal effects of blood and brain druggable expression quantitative trait loci (eQTLs) on AD. A repeat study was conducted using different blood and brain eQTL data sources to validate the identified genes. Using AD markers with available genome-wide association studies data, we evaluated the causal relationship between established AD markers to explore possible mechanisms. Finally, the potential side effects of the druggable genes for AD treatment were assessed using a phenome-wide MR.

resultsOverall, 5883 unique druggable genes were aggregated; 33 unique potential druggable genes for AD were identified in at least one dataset (brain or blood), and 5 were validated in a different dataset. Among them, three prior druggable genes (epoxide hydrolase 2 (

conclusionsThis study provides genetic evidence supporting the potential therapeutic benefits of targeting the three druggable genes for AD treatment, which will be useful for prioritising AD drug development.

Indexed as

Alzheimer DiseaseSerpinsBrainGenome-Wide Association StudyHippocampusHumansMendelian Randomization AnalysisPolymorphism, Single NucleotideSERPINB1 protein, humanSerpinsALZHEIMER'S DISEASECOGNITIONGENETICSMEDICINE

Identifiers

PMID37349091
PMCPMC10579488
OpenAlexW4381612968

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.