Evidence mapPaperPMID 40140823Full record

SynthesisLipids in health and disease2025

Druggable genome-wide Mendelian randomization identifies therapeutic targets for metabolic dysfunction-associated steatotic liver disease.

Xiaohui Ma, Li Ding, Shuo Li, Yu Fan, Xin Wang, Yitong Han, Hengjie Yuan, Longhao Sun, Qing He, Ming Liu

Abstract readMeta-Analysis
In one paragraph

Synthesis in Lipids in health and disease, 2025. 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. Review
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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.

Xiaohui Ma *Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
Li Ding *Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
Shuo Li *Department of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
Yu FanDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
Xin WangDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
Yitong HanDepartment of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.
Hengjie YuanDepartment of Pharmacy, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. hengjieyuan@163.com.
Longhao SunDepartment of General Surgery, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. sun_longhao@163.com.
Qing HeDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China. heqing202108@163.com.
Ming LiuDepartment of Endocrinology and Metabolism, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.

Funding

Major Project of Tianjin Municipal Science and Technology Bureau 21ZXJBSY00060the National Natural Science Foundation of China 82200882Tianjin Key Medical Discipline (Specialty) Construction Project TJYXZDXK-030ATianjin Major Science and Technology Projects 21ZXJBSY00050
6 · The paper itself

Abstract

backgroundMetabolic dysfunction-associated steatotic liver disease (MASLD) affects > 25% of the global population, potentially leading to severe hepatic and extrahepatic complications, including metabolic dysfunction-associated steatohepatitis. Given that the pathophysiology of MASLD is incompletely understood, identifying therapeutic targets and optimizing treatment strategies are crucial for addressing this severe condition.

methodsMendelian randomization (MR) analysis was conducted using two genome-wide association study datasets: a European meta-analysis (8,434 cases; 770,180 controls) and an additional study (3,954 cases; 355,942 controls), identifying therapeutic targets for MASLD. Of 4302 drug-target genes, 2,664 genetic instrument variables were derived from cis-expression quantitative trait loci (cis-eQTLs). Colocalization analyses assessed shared causal variants between MASLD-associated single nucleotide polymorphisms and eQTLs. Using the drug target gene cis-eQTL of liver tissue from the genotype-tissue expression project, we performed MR and summary MR to validate the significance of the gene results of the blood eQTL MR. RNA-sequencing data from liver biopsies were validated using immunohistochemistry and quantitative polymerase chain reaction (qPCR) tests to confirm gene expression findings.

resultMR analysis across both datasets identified significant MR associations between MASLD and two drug targets-milk fat globule-EGF factor 8 (MFGE8) (odds ratio [OR] 0.89, 95% confidence interval [CI] 0.85-0.94; P = 2.15 × 10

conclusionCD33 inhibition can reduce MASLD risk, while MFGE8 activation may offer therapeutic benefits for MASLD treatment.

Indexed as

Mendelian Randomization AnalysisMolecular Targeted TherapyNon-alcoholic Fatty Liver DiseaseGenome-Wide Association StudyHumansLiverPolymorphism, Single NucleotideQuantitative Trait LociCD33Mendelian randomization analysisMFGE8Non-alcoholic fatty liver diseaseNonalcoholic steatohepatitis

Identifiers

PMID40140823
PMCPMC11938603

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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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 Socratic graph.