ArticleArthritis research & therapy2017
Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis.
Article in Arthritis research & therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 31 citations in OpenAlex.
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- Identification of hub genes in rheumatoid arthritis through an integrated bioinformatics approach.Journal of orthopaedic surgery and research · 2021Article
- Disease severity-specific neutrophil signatures in blood transcriptomes stratify COVID-19 patients.Genome medicine · 2021Article
- Cross-Tissue Transcriptomic Analysis Leveraging Machine Learning Approaches Identifies New Biomarkers for Rheumatoid Arthritis.Frontiers in immunology · 2021Article
- Targeting MyD88 Downregulates Inflammatory Mediators and Pathogenic Processes in PBMC From DMARDs-Naïve Rheumatoid Arthritis Patients.Frontiers in pharmacology · 2021Article
- Thimet Oligopeptidase Biochemical and Biological Significances: Past, Present, and Future Directions.Biomolecules · 2020Review
- Genetic Polymorphisms Associated with Rheumatoid Arthritis Development and Antirheumatic Therapy Response.International journal of molecular sciences · 2020Review
- The Relevance of Thimet Oligopeptidase in the Regulation of Energy Metabolism and Diet-Induced Obesity.Biomolecules · 2020Article
- Novel Approaches and Challenges of Discovery of Exosite Modulators of a Disintegrin and Metalloprotease 10.Frontiers in molecular biosciences · 2020Review
- Thimet Oligopeptidase (EC 3.4.24.15) Key Functions Suggested by Knockout Mice Phenotype Characterization.Biomolecules · 2019Article
- Ancestry patterns inferred from massive RNA-seq data.RNA (New York, N.Y.) · 2019Article
- Thimet oligopeptidase as a potential CSF biomarker for Alzheimer's disease: A cross-platform validation study.Alzheimer's & dementia (Amsterdam, Netherlands)Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHere we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA).
methodRNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of "connector" genes derived from pathway analysis was tested for differential expression in the initial discovery cohort and validated in blood cells from 73 patients with RA and in 35 healthy controls.
resultsThere were 11 qualifying genes selected for pathway analysis and these were grouped into two evidence-based functional networks, containing 29 and 27 additional connector molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. Differences in the expression of ERBB2, TP53 and THOP1 were similar in both treated and non-treated patients with RA and an additional nine genes were differentially expressed in at least one group of patients compared to healthy controls. The ERBB2, TP53. THOP1 expression profile was successfully replicated in RNA-seq data from peripheral blood mononuclear cells from healthy controls and non-treated patients with RA, in an independent collection of samples.
conclusionIntegration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes, ERBB2, TP53 and THOP1 in the pathogenesis of RA.
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