Evidence map›Paper›PMID 38997544›Full record

ArticleClinical rheumatology2024

Prioritizing drug targets in systemic lupus erythematosus from a genetic perspective: a druggable genome-wide Mendelian randomization study.

Yuan Gao, Youtao Zhou, Zikai Lin, Fengzhen Chen, Haiyang Wu, Chusheng Peng, Yingying Xie

Abstract read
In one paragraph

Article in Clinical rheumatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
–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

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. 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

7 authors.

Yuan GaoThe First Clinical College, Guangzhou Medical University, Guangzhou, China.
Youtao ZhouThe First Clinical College, Guangzhou Medical University, Guangzhou, China.
Zikai LinNanshan College, Guangzhou Medical University, Guangzhou, China.
Fengzhen ChenThe First Clinical College, Guangzhou Medical University, Guangzhou, China.
Haiyang WuThe Second Clinical College, Guangzhou Medical University, Guangzhou, China.
Chusheng PengThe First Clinical College, Guangzhou Medical University, Guangzhou, China.
Yingying XieDepartment of Rheumatology and Immunology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, No. 151, Yanjiang West Road, Yuexiu District, Guangzhou, China. xieyingying423@163.com.ORCID http://orcid.org/0009-0004-5719-080X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectivesSystemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with an unsatisfactory state of treatment. We aim to explore novel targets for SLE from a genetic standpoint.

methodsCis-expression quantitative trait loci (eQTLs) for whole blood from 31,684 samples provided by the eQTLGen Consortium as well as two large SLE cohorts were utilized for screening and validating genes causally associated with SLE. Colocalization analysis was employed to further investigate whether changes in the expression of risk genes, as indicated by GWAS signals, influence the occurrence and development of SLE. Targets identified for drug development were evaluated for potential side effects using a phenome-wide association study (PheWAS). Based on the multiple databases, we explored the interactions between drugs and genes for drug prediction and the assessment of current medications.

resultsThe analysis comprised 5427 druggable genes in total. The two-sample Mendelian randomization (MR) in the discovery phase identified 20 genes causally associated with SLE and validated 8 genes in the replication phase. Colocalization analysis ultimately identified five genes (BLK, HIST1H3H, HSPA1A, IL12A, NEU1) with PPH4 > 0.8. PheWAS further indicated that drugs acting on BLK and IL12A are less likely to have potential side effects, while HSPA1A and NEU1 were associated with other traits. Four genes (BLK, HSPA1A, IL12A, NEU1) have been targeted for drug development in autoimmune diseases and other conditions.

conclusions.This study identified five genes as therapeutic targets for SLE. Repurposing and developing drugs targeting these genes is anticipated to improve the existing treatment state for SLE. Key Points • We identified five gene targets of priority for the treatment of SLE, with BLK and IL12A indicating fewer side effects. • Among the existing drugs that target these candidate genes, Ustekinumab, Ebdarokimab, and Briakinumab (targeting the IL12 gene) and CD24FC (targeting HSPA1A) may potentially be repurposed for the treatment of SLE.

Indexed as

Genome-Wide Association StudyHSP70 Heat-Shock ProteinsLupus Erythematosus, SystemicMendelian Randomization AnalysisQuantitative Trait LociGenetic Predisposition to DiseaseHumansInterleukin-12 Subunit p35Polymorphism, Single Nucleotidesrc-Family KinasesBLK protein, humanHSP70 Heat-Shock ProteinsHSPA1A protein, humanInterleukin-12 Subunit p35src-Family KinasesDrug targetExpression quantitative trait lociGeneticsMendelian randomizationSystemic lupus erythematosus

Identifiers

PMID38997544
PMCPMC11330408

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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.