Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation
Background: Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need to identify genes causally associated with IBD. Methods: We extracted blood eQTL data from the GTExv8.ALL.W...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | Heliyon |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844024049752 |
| _version_ | 1797217119695273984 |
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| author | Qinghua Luo Jiawen Wang Wei Ge Zihao Li Yuanting Mao Chen Wang Leichang Zhang |
| author_facet | Qinghua Luo Jiawen Wang Wei Ge Zihao Li Yuanting Mao Chen Wang Leichang Zhang |
| author_sort | Qinghua Luo |
| collection | DOAJ |
| description | Background: Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need to identify genes causally associated with IBD. Methods: We extracted blood eQTL data from the GTExv8.ALL.Whole_Blood database, genome-wide association studies (GWAS) summary statistics of IBD from the IEU GWAS database, and performed a three-fold analysis protocol, including transcriptome-wide association analysis, Mendelian randomisation analysis, Bayesian colocalisation, and subsequent potential therapeutic agents identification. Results: We identified four pathogenic genes, namely CARD9, RTEL1, STMN3 and ARFRP1, that promote the development of IBD, encompassing both ulcerative colitis (UC) and Crohn's disease (CD). Notably, ARFRP1 exhibited the ability to suppress IBD (encompassing UC and CD) development. Regarding drug prediction, cyclophosphamide emerged as a promising novel therapeutic option for IBD, encompassing UC and CD. Conclusion: We identified several potential genes related to IBD (UC and CD), including CARD9, RTEL1, STMN3 and ARFRP1, warranting further investigation in functional studies to elucidate underlying disease mechanisms. Additionally, clinical studies exploring the potential of cyclophosphamide as a treatment avenue for IBD are warranted. |
| first_indexed | 2024-04-24T11:56:48Z |
| format | Article |
| id | doaj.art-a537f2967e594b2ea7a339ed1aa010a0 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-24T11:56:48Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-a537f2967e594b2ea7a339ed1aa010a02024-04-09T04:13:22ZengElsevierHeliyon2405-84402024-04-01107e28944Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisationQinghua Luo0Jiawen Wang1Wei Ge2Zihao Li3Yuanting Mao4Chen Wang5Leichang Zhang6Clinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, ChinaDepartment of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Proctology, Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang, ChinaOffice of the President, Jiangmen Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, ChinaClinical Medical College, Jiangxi University of Chinese Medicine, Nanchang, ChinaDepartment of Proctology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China; Corresponding author.Formula-Pattern Research Center, Jiangxi University of Chinese Medicine, Jiangxi, China; Corresponding author.Background: Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need to identify genes causally associated with IBD. Methods: We extracted blood eQTL data from the GTExv8.ALL.Whole_Blood database, genome-wide association studies (GWAS) summary statistics of IBD from the IEU GWAS database, and performed a three-fold analysis protocol, including transcriptome-wide association analysis, Mendelian randomisation analysis, Bayesian colocalisation, and subsequent potential therapeutic agents identification. Results: We identified four pathogenic genes, namely CARD9, RTEL1, STMN3 and ARFRP1, that promote the development of IBD, encompassing both ulcerative colitis (UC) and Crohn's disease (CD). Notably, ARFRP1 exhibited the ability to suppress IBD (encompassing UC and CD) development. Regarding drug prediction, cyclophosphamide emerged as a promising novel therapeutic option for IBD, encompassing UC and CD. Conclusion: We identified several potential genes related to IBD (UC and CD), including CARD9, RTEL1, STMN3 and ARFRP1, warranting further investigation in functional studies to elucidate underlying disease mechanisms. Additionally, clinical studies exploring the potential of cyclophosphamide as a treatment avenue for IBD are warranted.http://www.sciencedirect.com/science/article/pii/S2405844024049752 |
| spellingShingle | Qinghua Luo Jiawen Wang Wei Ge Zihao Li Yuanting Mao Chen Wang Leichang Zhang Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation Heliyon |
| title | Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation |
| title_full | Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation |
| title_fullStr | Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation |
| title_full_unstemmed | Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation |
| title_short | Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation |
| title_sort | exploration of the potential causative genes for inflammatory bowel disease transcriptome wide association analysis mendelian randomization analysis and bayesian colocalisation |
| url | http://www.sciencedirect.com/science/article/pii/S2405844024049752 |
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