Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysis
Abstract Mitochondrial DNA plays a critical role in the pathophysiological process of inflammation. However, the relationship between mitochondrial DNA copy number (mtDNA-CN) and inflammatory bowel diseases (IBD) remains poorly understood. We conducted a comprehensive Mendelian randomization (MR) us...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2023-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-48175-5 |
| _version_ | 1797415214401978368 |
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| author | Xianlei Cai Xueying Li Chao Liang Miaozun Zhang Yuan Xu Zhebin Dong Yihui Weng Weiming Yu |
| author_facet | Xianlei Cai Xueying Li Chao Liang Miaozun Zhang Yuan Xu Zhebin Dong Yihui Weng Weiming Yu |
| author_sort | Xianlei Cai |
| collection | DOAJ |
| description | Abstract Mitochondrial DNA plays a critical role in the pathophysiological process of inflammation. However, the relationship between mitochondrial DNA copy number (mtDNA-CN) and inflammatory bowel diseases (IBD) remains poorly understood. We conducted a comprehensive Mendelian randomization (MR) using three instrumental variables (IVs) to explore the causal associations between mtDNA-CN and IBD, including Crohn's disease (CD), ulcerative colitis (UC). MR-Egger regression, weighted median, inverse-variance weighted (IVW), and weighted mode methods were used to evaluate the potential causal associations. The robustness of the IVW estimates was determined using the leave-one-out sensitivity test. A meta-analysis was conducted to pool the results from the three sets of IVs. Upon analysis, the findings of the current study revealed that genetically predicted mtDNA-CN was not associated with IBD (CD + UC) and UC. The results of MR analyses between mtDNA-CN and CD risk were inconsistent by using three sets of IVs. After a meta-analysis, we found that genetically predicted mtDNA-CN was associated with CD risk (odds ratio = 2.09; 95% confidence interval: 1.37–3.18). This finding was also confirmed by multivariable MR analyses and remained robust when tested with the leave-one-out sensitivity test. In conclusion, genetically predicted mtDNA-CN was found to be associated with CD risk. Therefore, mtDNA levels in the blood could potentially be used as a marker for CD risk assessment. Further studies are needed to elucidate the underlying mechanisms and validate the results of this study. |
| first_indexed | 2024-03-09T05:44:37Z |
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| id | doaj.art-ddb564bcd7be4938969d35a236ca9bb5 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T05:44:37Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-ddb564bcd7be4938969d35a236ca9bb52023-12-03T12:22:25ZengNature PortfolioScientific Reports2045-23222023-11-0113111010.1038/s41598-023-48175-5Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysisXianlei Cai0Xueying Li1Chao Liang2Miaozun Zhang3Yuan Xu4Zhebin Dong5Yihui Weng6Weiming Yu7Department of Gastrointestinal Surgery, The Lihuili Affiliated Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital)Department of Gastroenterology, The First Affiliated Hospital, Ningbo UniversityDepartment of Gastrointestinal Surgery, The Lihuili Affiliated Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital)Department of Gastrointestinal Surgery, The Lihuili Affiliated Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital)Department of Gastrointestinal Surgery, The Lihuili Affiliated Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital)Department of Gastrointestinal Surgery, The Lihuili Affiliated Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital)Department of Gastrointestinal Surgery, The Lihuili Affiliated Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital)Department of Gastrointestinal Surgery, The Lihuili Affiliated Hospital, Ningbo University (Ningbo Medical Center Lihuili Hospital)Abstract Mitochondrial DNA plays a critical role in the pathophysiological process of inflammation. However, the relationship between mitochondrial DNA copy number (mtDNA-CN) and inflammatory bowel diseases (IBD) remains poorly understood. We conducted a comprehensive Mendelian randomization (MR) using three instrumental variables (IVs) to explore the causal associations between mtDNA-CN and IBD, including Crohn's disease (CD), ulcerative colitis (UC). MR-Egger regression, weighted median, inverse-variance weighted (IVW), and weighted mode methods were used to evaluate the potential causal associations. The robustness of the IVW estimates was determined using the leave-one-out sensitivity test. A meta-analysis was conducted to pool the results from the three sets of IVs. Upon analysis, the findings of the current study revealed that genetically predicted mtDNA-CN was not associated with IBD (CD + UC) and UC. The results of MR analyses between mtDNA-CN and CD risk were inconsistent by using three sets of IVs. After a meta-analysis, we found that genetically predicted mtDNA-CN was associated with CD risk (odds ratio = 2.09; 95% confidence interval: 1.37–3.18). This finding was also confirmed by multivariable MR analyses and remained robust when tested with the leave-one-out sensitivity test. In conclusion, genetically predicted mtDNA-CN was found to be associated with CD risk. Therefore, mtDNA levels in the blood could potentially be used as a marker for CD risk assessment. Further studies are needed to elucidate the underlying mechanisms and validate the results of this study.https://doi.org/10.1038/s41598-023-48175-5 |
| spellingShingle | Xianlei Cai Xueying Li Chao Liang Miaozun Zhang Yuan Xu Zhebin Dong Yihui Weng Weiming Yu Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysis Scientific Reports |
| title | Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysis |
| title_full | Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysis |
| title_fullStr | Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysis |
| title_full_unstemmed | Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysis |
| title_short | Mitochondrial DNA copy number is associated with Crohn’s disease: a comprehensive Mendelian randomization analysis |
| title_sort | mitochondrial dna copy number is associated with crohn s disease a comprehensive mendelian randomization analysis |
| url | https://doi.org/10.1038/s41598-023-48175-5 |
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