Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles
Abstract Aim Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with genetic susceptibility and pathological processes such as autoimmunity and autoinflammation, but its pathogenesis is unclear. We conducted a transcriptome-wide association study (TWAS) us...
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| Format: | Article |
| Language: | English |
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BMC
2023-02-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13075-023-03003-z |
| _version_ | 1811165798771720192 |
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| author | Ruoyang Feng Mengnan Lu Chunyan Yin Ke Xu Lin Liu Peng Xu |
| author_facet | Ruoyang Feng Mengnan Lu Chunyan Yin Ke Xu Lin Liu Peng Xu |
| author_sort | Ruoyang Feng |
| collection | DOAJ |
| description | Abstract Aim Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with genetic susceptibility and pathological processes such as autoimmunity and autoinflammation, but its pathogenesis is unclear. We conducted a transcriptome-wide association study (TWAS) using expression interpolation from a large-scale genome-wide association study (GWAS) dataset to identify genes, biological pathways, and environmental chemicals associated with JIA. Methods We obtained published GWAS data on JIA for TWAS and used mRNA expression profiling to validate the genes identified by TWAS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A protein–protein interaction (PPI) network was generated, and central genes were obtained using Molecular Complex Detection (MCODE). Finally, chemical gene expression datasets were obtained from the Comparative Toxicogenomics database for chemical genome enrichment analysis. Results TWAS identified 1481 genes associated with JIA, and 154 differentially expressed genes were identified based on mRNA expression profiles. After comparing the results of TWAS and mRNA expression profiles, we obtained eight overlapping genes. GO and KEGG enrichment analyses of the genes identified by TWAS yielded 163 pathways, and PPI network analysis as well as MCODE resolution identified a total of eight clusters. Through chemical gene set enrichment analysis, 287 environmental chemicals associated with JIA were identified. Conclusion By integrating TWAS and mRNA expression profiles, genes, biological pathways, and environmental chemicals associated with JIA were identified. Our findings provide new insights into the pathogenesis of JIA, including candidate genetic and environmental factors contributing to its onset and progression. |
| first_indexed | 2024-04-10T15:42:29Z |
| format | Article |
| id | doaj.art-d34f5a2c8854424fb06855570cf7abfd |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-04-10T15:42:29Z |
| publishDate | 2023-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-d34f5a2c8854424fb06855570cf7abfd2023-02-12T12:18:48ZengBMCArthritis Research & Therapy1478-63622023-02-0125111310.1186/s13075-023-03003-zIdentification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profilesRuoyang Feng0Mengnan Lu1Chunyan Yin2Ke Xu3Lin Liu4Peng Xu5Department of Joint Surgery, HongHui Hospital, Xian Jiaotong UniversityDepartment of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Pediatrics, The Second Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Joint Surgery, HongHui Hospital, Xian Jiaotong UniversityDepartment of Joint Surgery, HongHui Hospital, Xian Jiaotong UniversityDepartment of Joint Surgery, HongHui Hospital, Xian Jiaotong UniversityAbstract Aim Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease of childhood, with genetic susceptibility and pathological processes such as autoimmunity and autoinflammation, but its pathogenesis is unclear. We conducted a transcriptome-wide association study (TWAS) using expression interpolation from a large-scale genome-wide association study (GWAS) dataset to identify genes, biological pathways, and environmental chemicals associated with JIA. Methods We obtained published GWAS data on JIA for TWAS and used mRNA expression profiling to validate the genes identified by TWAS. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. A protein–protein interaction (PPI) network was generated, and central genes were obtained using Molecular Complex Detection (MCODE). Finally, chemical gene expression datasets were obtained from the Comparative Toxicogenomics database for chemical genome enrichment analysis. Results TWAS identified 1481 genes associated with JIA, and 154 differentially expressed genes were identified based on mRNA expression profiles. After comparing the results of TWAS and mRNA expression profiles, we obtained eight overlapping genes. GO and KEGG enrichment analyses of the genes identified by TWAS yielded 163 pathways, and PPI network analysis as well as MCODE resolution identified a total of eight clusters. Through chemical gene set enrichment analysis, 287 environmental chemicals associated with JIA were identified. Conclusion By integrating TWAS and mRNA expression profiles, genes, biological pathways, and environmental chemicals associated with JIA were identified. Our findings provide new insights into the pathogenesis of JIA, including candidate genetic and environmental factors contributing to its onset and progression.https://doi.org/10.1186/s13075-023-03003-zJuvenile idiopathic arthritisGWASTWASEnvironment factorsSusceptibility gene |
| spellingShingle | Ruoyang Feng Mengnan Lu Chunyan Yin Ke Xu Lin Liu Peng Xu Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles Arthritis Research & Therapy Juvenile idiopathic arthritis GWAS TWAS Environment factors Susceptibility gene |
| title | Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles |
| title_full | Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles |
| title_fullStr | Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles |
| title_full_unstemmed | Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles |
| title_short | Identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome-wide association studies and mRNA expression profiles |
| title_sort | identification of candidate genes and pathways associated with juvenile idiopathic arthritis by integrative transcriptome wide association studies and mrna expression profiles |
| topic | Juvenile idiopathic arthritis GWAS TWAS Environment factors Susceptibility gene |
| url | https://doi.org/10.1186/s13075-023-03003-z |
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