Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study
Abstract Background Previous research has established a correlation between immune cells and an increased likelihood of Chronic pancreatitis (CP). However, studies investigating the causal relationship remain limited. Methods This study utilized publicly available genome-wide association study (GWAS...
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BMC
2025-02-01
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| Series: | Hereditas |
| Online Access: | https://doi.org/10.1186/s41065-025-00378-8 |
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| author | Chao Zhang Tao Yang Yuan Yu Qian Jia Wan-Meng Xiao Sha Liu Ze-Hui Yu Cheng-Li Wen Yan Wei Hao Li Mu-Han Lü |
| author_facet | Chao Zhang Tao Yang Yuan Yu Qian Jia Wan-Meng Xiao Sha Liu Ze-Hui Yu Cheng-Li Wen Yan Wei Hao Li Mu-Han Lü |
| author_sort | Chao Zhang |
| collection | DOAJ |
| description | Abstract Background Previous research has established a correlation between immune cells and an increased likelihood of Chronic pancreatitis (CP). However, studies investigating the causal relationship remain limited. Methods This study utilized publicly available genome-wide association study (GWAS) databases and conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationships (CRs) among 731 immune cells, 1,400 metabolites, and CP. Mediation MR analysis was also performed to assess whether metabolites serve as mediators in the relationship between immune cells and CP. Results Our study identified four immune cell types that act as risk factors for CP, with odds ratios (OR) ranging between 1.076 and 1.177. In contrast, three immune cell types were found to serve as protective factors, exhibiting OR values between 0.846 and 0.913. Additionally, four metabolites were implicated as risk factors for CP, with OR values ranging from 1.243 to 1.334. On the other hand, eight metabolites were discovered to have a protective effect, with OR values between 0.580 and 0.871. Mediation analysis revealed that cholesterol levels mediate the causal relationship between immune cell cells and CP, with a mediation effect of 0.00918, accounting for 9.18% of the total effect. Conclusions Our findings provide valuable insights into the genetic underpinnings of CP, highlighting the role of immune cells and plasma metabolites in its pathogenesis. The mediation analysis further suggests that the presence of CD25 on IgD-CD38-B cells may facilitate CP development through the elevation of cholesterol levels. These results not only deepen our understanding of CP but also suggest potential biological targets for therapeutic intervention. Future clinical research should focus on these mediators to develop more effective treatment strategies for CP. |
| format | Article |
| id | doaj-art-68ede1d57e554d46b4534466ef8e4b99 |
| institution | OA Journals |
| issn | 1601-5223 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Hereditas |
| spelling | doaj-art-68ede1d57e554d46b4534466ef8e4b992025-08-20T02:13:06ZengBMCHereditas1601-52232025-02-01162111210.1186/s41065-025-00378-8Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization studyChao Zhang0Tao Yang1Yuan Yu2Qian Jia3Wan-Meng Xiao4Sha Liu5Ze-Hui Yu6Cheng-Li Wen7Yan Wei8Hao Li9Mu-Han Lü10Department of Gastroenterology, The Affiliated Hospital, Southwest Medical UniversityDepartment of Gastroenterology, The Affiliated Hospital, Southwest Medical UniversityGulin County People’s HospitalDepartment of Gastroenterology, The Affiliated Hospital, Southwest Medical UniversityDepartment of Gastroenterology, The Affiliated Hospital, Southwest Medical UniversityDepartment of Gastroenterology, The Affiliated Hospital, Southwest Medical UniversityLaboratory Animal Center, Southwest Medical UniversityDepartment of Critical Care Medicine, The Affiliated Hospital, Southwest Medical UniversityKey Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, Collaborative Innovation Center for Prevention of Cardiovascular Diseases), Institute of Cardiovascular Research, Southwest Medical UniversityDepartment of Gastroenterology, The Affiliated Hospital, Southwest Medical UniversityDepartment of Gastroenterology, The Affiliated Hospital, Southwest Medical UniversityAbstract Background Previous research has established a correlation between immune cells and an increased likelihood of Chronic pancreatitis (CP). However, studies investigating the causal relationship remain limited. Methods This study utilized publicly available genome-wide association study (GWAS) databases and conducted a two-sample Mendelian randomization (MR) analysis to examine the causal relationships (CRs) among 731 immune cells, 1,400 metabolites, and CP. Mediation MR analysis was also performed to assess whether metabolites serve as mediators in the relationship between immune cells and CP. Results Our study identified four immune cell types that act as risk factors for CP, with odds ratios (OR) ranging between 1.076 and 1.177. In contrast, three immune cell types were found to serve as protective factors, exhibiting OR values between 0.846 and 0.913. Additionally, four metabolites were implicated as risk factors for CP, with OR values ranging from 1.243 to 1.334. On the other hand, eight metabolites were discovered to have a protective effect, with OR values between 0.580 and 0.871. Mediation analysis revealed that cholesterol levels mediate the causal relationship between immune cell cells and CP, with a mediation effect of 0.00918, accounting for 9.18% of the total effect. Conclusions Our findings provide valuable insights into the genetic underpinnings of CP, highlighting the role of immune cells and plasma metabolites in its pathogenesis. The mediation analysis further suggests that the presence of CD25 on IgD-CD38-B cells may facilitate CP development through the elevation of cholesterol levels. These results not only deepen our understanding of CP but also suggest potential biological targets for therapeutic intervention. Future clinical research should focus on these mediators to develop more effective treatment strategies for CP.https://doi.org/10.1186/s41065-025-00378-8 |
| spellingShingle | Chao Zhang Tao Yang Yuan Yu Qian Jia Wan-Meng Xiao Sha Liu Ze-Hui Yu Cheng-Li Wen Yan Wei Hao Li Mu-Han Lü Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study Hereditas |
| title | Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study |
| title_full | Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study |
| title_fullStr | Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study |
| title_full_unstemmed | Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study |
| title_short | Causal roles of immune cells and metabolites in chronic pancreatitis: a mendelian randomization study |
| title_sort | causal roles of immune cells and metabolites in chronic pancreatitis a mendelian randomization study |
| url | https://doi.org/10.1186/s41065-025-00378-8 |
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