Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity
Abstract Background Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical re...
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BMC
2024-02-01
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| Series: | BMC Genomics |
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| Online Access: | https://doi.org/10.1186/s12864-024-10003-z |
| _version_ | 1797275750201556992 |
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| author | Mengfen Huang Yuan Wu Yiting Li Xueru Chen Jieni Feng Zuming Li Jiqiang Li Jiankun Chen Yue Lu Yan Feng |
| author_facet | Mengfen Huang Yuan Wu Yiting Li Xueru Chen Jieni Feng Zuming Li Jiqiang Li Jiankun Chen Yue Lu Yan Feng |
| author_sort | Mengfen Huang |
| collection | DOAJ |
| description | Abstract Background Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. Methods Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). Results Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. Conclusions This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets. |
| first_indexed | 2024-03-07T15:18:53Z |
| format | Article |
| id | doaj.art-4f4e2f85a6b54f48b829a37a207ebf08 |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-03-07T15:18:53Z |
| publishDate | 2024-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-4f4e2f85a6b54f48b829a37a207ebf082024-03-05T17:46:48ZengBMCBMC Genomics1471-21642024-02-0125111010.1186/s12864-024-10003-zCircadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidityMengfen Huang0Yuan Wu1Yiting Li2Xueru Chen3Jieni Feng4Zuming Li5Jiqiang Li6Jiankun Chen7Yue Lu8Yan Feng9Guangzhou University of Chinese MedicineThe Second Clinical Medical College, Guangzhou University of Chinese MedicineThe First Clinical Medical College, Guangzhou University of Chinese MedicineThe Second Clinical Medical College, Guangzhou University of Chinese MedicineThe Second Clinical Medical College, Guangzhou University of Chinese MedicineThe Second Clinical Medical College, Guangzhou University of Chinese MedicineThe Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)The Second Affiliated Hospital of Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine)Abstract Background Circadian rhythm is crucial to the function of the immune system. Disorders of the circadian rhythm can contribute to inflammatory diseases such as Ulcerative colitis (UC). This Mendelian Randomization (MR) analysis applies genetic tools to represent the aggregated statistical results of exposure to circadian rhythm disorders and UC and its comorbidities, allowing for causal inferences. Methods Summary statistics of protein, DNA methylation and gene expression quantitative trait loci in individuals of European ancestry (pQTL, mQTL, and eQTL, respectively) were used. Genetic variants located within or near 152 circadian clock-related genes and closely related to circadian rhythm disorders were selected as instrumental variables. Causal relationships with UC and its comorbidities were then estimated through employed Summary data-based Mendelian Randomization (SMR) and Inverse-Variance-Weighted MR (IVW-MR). Results Through preliminary SMR analysis, we identified a potential causal relationship between circadian clock-related genes and UC along with its comorbidities, which was further confirmed by IVW-MR analysis. Our study identified strong evidence of positive correlation involving seven overlapping genes (CSNK1E, OPRL1, PIWIL2, RORC, MAX, PPP5C, and AANAT) through MWAS and TWAS in UC, four overlapping genes (OPRL1, CHRNB2, FBXL17, and SIRT1) in UC with PSC, and three overlapping genes (ARNTL, USP7, and KRAS) in UC with arthropathy. Conclusions This SMR study demonstrates the causal effect of circadian rhythm disorders in UC and its comorbidities. Furthermore, our investigation pinpointed candidate genes that could potentially serve as drug targets.https://doi.org/10.1186/s12864-024-10003-zMendelian randomizationCircadian rhythm disorderUC and its comorbiditiesPharmaceutical targets |
| spellingShingle | Mengfen Huang Yuan Wu Yiting Li Xueru Chen Jieni Feng Zuming Li Jiqiang Li Jiankun Chen Yue Lu Yan Feng Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity BMC Genomics Mendelian randomization Circadian rhythm disorder UC and its comorbidities Pharmaceutical targets |
| title | Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity |
| title_full | Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity |
| title_fullStr | Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity |
| title_full_unstemmed | Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity |
| title_short | Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity |
| title_sort | circadian clock related genome wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity |
| topic | Mendelian randomization Circadian rhythm disorder UC and its comorbidities Pharmaceutical targets |
| url | https://doi.org/10.1186/s12864-024-10003-z |
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