Evidence map›Paper›PMID 38809509›Full record

ArticleAging2024

Leveraging pQTL-based Mendelian randomization to identify new treatment prospects for primary biliary cholangitis and primary sclerosing cholangitis.

Lei Dai, Yunyan Ye, Joseph Mugaany, Zetong Hu, Jing Huang, Changjiang Lu

Abstract read
In one paragraph

Article in Aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. 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

6 authors.

Lei DaiDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Centre Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315040, China.
Yunyan YeDepartment of Ophthalmology, Ningbo Medical Centre Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315040, China.
Joseph MugaanyDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Centre Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315040, China.
Zetong HuDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Centre Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315040, China.
Jing HuangDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Centre Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315040, China.
Changjiang LuDepartment of Hepato-Pancreato-Biliary Surgery, Ningbo Medical Centre Lihuili Hospital, The Affiliated Hospital of Ningbo University, Ningbo, Zhejiang 315040, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune disorders characterized by progressive and chronic damage to the bile ducts, presenting clinicians with significant challenges. The objective of this study is to identify potential druggable targets to offer new avenues for treatment. A Mendelian randomization analysis was performed to identify druggable targets for PBC and PSC. This involved obtaining Cis-protein quantitative trait loci (Cis-pQTL) data from the deCODE database to serve as exposure. Outcome data for PBC (557 cases and 281,127 controls) and PSC (1,715 cases and 330,903 controls) were obtained from the FINNGEN database. Colocalization analysis was conducted to determine whether these features share the same associated SNPs. Validation of the expression level of druggable targets was done using the GSE119600 dataset and immunohistochemistry for clinical samples. Lastly, the DRUGBANK database was used to predict potential drugs. The MR analysis identified eight druggable targets each for PBC and PSC. Subsequent summary-data-based MR and colocalization analyses showed that LEFTY2 had strong evidence as a therapeutic candidate for PBC, while HSPB1 had moderate evidence. For PSC, only FCGR3B showed strong evidence as a therapeutic candidate. Additionally, upregulated expression of these genes was validated in PBC and PSC groups by GEO dataset and clinical samples. This study identifies two novel druggable targets with strong evidence for therapeutic candidates for PBC (LEFTY2 and HSPB1) and one for PSC (FCGR3B). These targets offer new therapeutic opportunities to address the challenging nature of PBC and PSC treatment.

Indexed as

Cholangitis, SclerosingLiver Cirrhosis, BiliaryMendelian Randomization AnalysisQuantitative Trait LociDatabases, GeneticHumansPolymorphism, Single NucleotidedrugMendelian randomizationprimary biliary cholangitisprimary sclerosing cholangitisSNPs

Identifiers

PMID38809509
PMCPMC11164478

What OpenQuestion holds

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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.