ArticleBrain communications2020
Summary-data-based Mendelian randomization prioritizes potential druggable targets for multiple sclerosis.
Article in Brain communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Oxidative stress gene expression, DNA methylation, and gut microbiota interaction trigger Crohn's disease: a multi-omics Mendelian randomization study.BMC medicine · 2023Pooled it
- Genome-Wide Gene-Set Analysis Identifies Molecular Mechanisms Associated with ALS.International journal of molecular sciences · 2023Pooled it
- LocusPackRat: an R package to support prioritizing candidate genes from large GWAS intervals with standardized evidence aggregation.G3 (Bethesda, Md.) · 2026Article
- Identification of key genes as diagnostic biomarkers for lung adenocarcinoma using bioinformatics and machine learning.Discover oncology · 2026Article
- Crotonylation and the Risk of Head and Neck Cancer: Insights from a Two-Sample Mendelian Randomization Study.International dental journal · 2026Article
- Genetic associations in sepsis and ARDS.Frontiers in pharmacology · 2026Review
- Integrating network pharmacology with molecular docking and dynamics to uncover therapeutic targets and signaling mechanisms of vitamin D3 in Parkinson's disease.Molecular diversity · 2025Article
- Enhancing Chemosensitivity With Quercetin: Mechanistic Insights Into MerTK and Associated Signaling Pathways.Cancer reports (Hoboken, N.J.) · 2025Review
- Mendelian randomization identifies proteins involved in neurodegenerative diseases.Brain : a journal of neurology · 2025Article
- Multiomics integration prioritizes potential drug targets for multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Neuroprotective strategies in multiple sclerosis: a status update and emerging paradigms.Expert review of neurotherapeutics · 2025Review
- Single-cell analysis of cerebrospinal fluid reveals common features of neuroinflammation.Cell reports. Medicine · 2025Article
- DNA Methylation-Mediated Downregulation ofInternational journal of chronic obstructive pulmonary disease · 2025Article
- Identifying genetically-supported drug repurposing targets for non-small cell lung cancer through mendelian randomization of the druggable genome.Translational lung cancer research · 2024Article
- An Overview of Epigenetic Changes in the Parkinson's Disease Brain.International journal of molecular sciences · 2024Review
- Integrated analyses of single-cell transcriptome and Mendelian randomization reveal the protective role of FCRL3 in multiple sclerosis.Frontiers in immunology · 2024Article
- Whole-genome sequencing analysis of suicide deaths integrating brain-regulatory eQTLs data to identify risk loci and genes.Molecular psychiatry · 2023Article
- Potential drug targets for multiple sclerosis identified through Mendelian randomization analysis.Brain : a journal of neurology · 2023Article
- Endoplasmic reticulum stress related genome-wide Mendelian randomization identifies therapeutic genes for ulcerative colitis and Crohn's disease.Frontiers in genetics · 2023Article
- Omics approaches to understanding the efficacy and safety of disease-modifying treatments in multiple sclerosis.Frontiers in genetics · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Multiple sclerosis is a complex autoimmune disease caused by a combination of genetic and environmental factors. Translation of Genome-Wide Association Study findings into therapeutics and effective preventive strategies has been limited to date. We used summary-data-based Mendelian randomization to synthesize findings from public expression quantitative trait locus, methylation quantitative trait locus and Multiple Sclerosis Genome-Wide Association Study datasets. By correlating the effects of methylation on multiple sclerosis, methylation on expression and expression on multiple sclerosis susceptibility, we prioritize genetic loci with evidence of influencing multiple sclerosis susceptibility. We overlay these findings onto a list of 'druggable' genes, i.e. genes which are currently, or could theoretically, be targeted by therapeutic compounds. We use GeNets and search tool for the retrieval of interacting genes/proteins to identify protein-protein interactions and druggable pathways enriched in our results. We extend these findings to a model of Epstein-Barr virus-infected B cells, lymphoblastoid cell lines. We conducted a systematic review of prioritized genes using the Open Targets platform to identify completed and planned trials targeting prioritized genes in multiple sclerosis and related disease areas. Expression of 45 genes in peripheral blood was strongly associated with multiple sclerosis susceptibility (False discovery rate 0.05). Of these 45 genes, 20 encode a protein which is currently targeted by an existing therapeutic compound. These genes were enriched for Gene Ontology terms pertaining to immune system function and leucocyte signalling. We refined this prioritized gene list by restricting to loci where CpG site methylation was associated with multiple sclerosis susceptibility, with gene expression and where expression was associated with multiple sclerosis susceptibility. This approach yielded a list of 15 prioritized druggable target genes for which there was evidence of a pathway linking methylation, expression and multiple sclerosis. Five of these 15 genes are targeted by existing drugs and three were replicated in a smaller expression Quantitative Trait Loci dataset (
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Registered trials
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.