Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics
Abstract With the rapid advancement of proteomics, numerous scholars have investigated the intricate relationships between plasma proteins and various diseases. Therefore, this study aims to elucidate the relationship between BDH1 and type 2 diabetes using Mendelian randomization (MR) and to identif...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-88196-w |
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| author | Yi-Ying Liu Yue-Yang Zhang Qin Wan |
| author_facet | Yi-Ying Liu Yue-Yang Zhang Qin Wan |
| author_sort | Yi-Ying Liu |
| collection | DOAJ |
| description | Abstract With the rapid advancement of proteomics, numerous scholars have investigated the intricate relationships between plasma proteins and various diseases. Therefore, this study aims to elucidate the relationship between BDH1 and type 2 diabetes using Mendelian randomization (MR) and to identify novel targets for the prevention and treatment of type 2 diabetes through proteomics. This study primarily employed the Mendelian Randomization (MR) method, leveraging genetic data from numerous large-scale, publicly accessible genome-wide association studies (GWAS). Within this framework, we adopted a two-step, two-sample MR approach to evaluate the relationships between BDH1, plasma proteins, and type 2 diabetes. Finally, we conducted bidirectional MR analyses along with various sensitivity analyses to ensure the robustness and reliability of the study findings. The inverse variance weighted (IVW) analysis demonstrated that for each 1 standard deviation (SD) increase in BDH1, the risk of type 2 diabetes decreased by 3% (OR: 0.97; 95% CI: 0.95, 0.99). Concurrently, the proteomics-based MR analysis identified 37 plasma proteins associated with type 2 diabetes and 27 plasma proteins associated with BDH1. Notably, NBN, ARG1, and CCL11 were found to mediate the protective effect of BDH1 on type 2 diabetes. Our research findings uncovered the potential protective effect of BDH1 on type 2 diabetes and identified several plasma proteins associated with the disease. These results open new avenues for enhanced exploration of the prevention and treatment of type 2 diabetes. |
| format | Article |
| id | doaj-art-9ef98c3525d84663bb52ba2a18907e26 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-9ef98c3525d84663bb52ba2a18907e262025-02-02T12:17:05ZengNature PortfolioScientific Reports2045-23222025-01-011511710.1038/s41598-025-88196-wInterconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomicsYi-Ying Liu0Yue-Yang Zhang1Qin Wan2Centre for Endocrine and Thyroid Diseases, Deyang People’s HospitalDepartment of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical UniversityDepartment of Endocrinology and Metabolism, Affiliated Hospital of Southwest Medical UniversityAbstract With the rapid advancement of proteomics, numerous scholars have investigated the intricate relationships between plasma proteins and various diseases. Therefore, this study aims to elucidate the relationship between BDH1 and type 2 diabetes using Mendelian randomization (MR) and to identify novel targets for the prevention and treatment of type 2 diabetes through proteomics. This study primarily employed the Mendelian Randomization (MR) method, leveraging genetic data from numerous large-scale, publicly accessible genome-wide association studies (GWAS). Within this framework, we adopted a two-step, two-sample MR approach to evaluate the relationships between BDH1, plasma proteins, and type 2 diabetes. Finally, we conducted bidirectional MR analyses along with various sensitivity analyses to ensure the robustness and reliability of the study findings. The inverse variance weighted (IVW) analysis demonstrated that for each 1 standard deviation (SD) increase in BDH1, the risk of type 2 diabetes decreased by 3% (OR: 0.97; 95% CI: 0.95, 0.99). Concurrently, the proteomics-based MR analysis identified 37 plasma proteins associated with type 2 diabetes and 27 plasma proteins associated with BDH1. Notably, NBN, ARG1, and CCL11 were found to mediate the protective effect of BDH1 on type 2 diabetes. Our research findings uncovered the potential protective effect of BDH1 on type 2 diabetes and identified several plasma proteins associated with the disease. These results open new avenues for enhanced exploration of the prevention and treatment of type 2 diabetes.https://doi.org/10.1038/s41598-025-88196-w3-hydroxybutyrate dehydrogenase 1Type 2 diabetesProteomicsMendelian randomizationMediation effect |
| spellingShingle | Yi-Ying Liu Yue-Yang Zhang Qin Wan Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics Scientific Reports 3-hydroxybutyrate dehydrogenase 1 Type 2 diabetes Proteomics Mendelian randomization Mediation effect |
| title | Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics |
| title_full | Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics |
| title_fullStr | Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics |
| title_full_unstemmed | Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics |
| title_short | Interconnections between BDH1-plasma protein-type 2 diabetes Mellitus: a mediated mendelian randomization analysis using plasma proteomics |
| title_sort | interconnections between bdh1 plasma protein type 2 diabetes mellitus a mediated mendelian randomization analysis using plasma proteomics |
| topic | 3-hydroxybutyrate dehydrogenase 1 Type 2 diabetes Proteomics Mendelian randomization Mediation effect |
| url | https://doi.org/10.1038/s41598-025-88196-w |
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