Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis
Abstract Background Diabetic polyneuropathy (DPN) is a common diabetes complication with limited treatment options. We aimed to identify circulating plasma proteins as potential therapeutic targets for DPN using Mendelian Randomization (MR). Methods The protein quantitative trait loci (pQTLs) utiliz...
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BMC
2024-12-01
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| Online Access: | https://doi.org/10.1186/s13578-024-01323-4 |
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| author | Xiaokun Chen Guohua Jiang Tianjing Zhao Nian Sun Shanshan Liu Hao Guo Canjun Zeng Yijun Liu |
| author_facet | Xiaokun Chen Guohua Jiang Tianjing Zhao Nian Sun Shanshan Liu Hao Guo Canjun Zeng Yijun Liu |
| author_sort | Xiaokun Chen |
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| description | Abstract Background Diabetic polyneuropathy (DPN) is a common diabetes complication with limited treatment options. We aimed to identify circulating plasma proteins as potential therapeutic targets for DPN using Mendelian Randomization (MR). Methods The protein quantitative trait loci (pQTLs) utilized in this study were derived from seven previously published genome-wide association studies (GWASs) on plasma proteomics. The DPN data were obtained from the IEU OpenGWAS project. This study employed two-sample MR using MR-Egger and inverse-variance weighted methods to evaluate the causal relationship between plasma proteins and DPN risk, with Cochran’s Q test, and I2 statistics, among other methods, used to validate the robustness of the results. Results Using cis-pQTLs as genetic instruments, we identified 62 proteins associated with DPN, with 33 increasing the risk and 29 decreasing the risk of DPN. Using cis-pQTLs + trans-pQTLs, we identified 116 proteins associated with DPN, with 44 increasing the risk and 72 decreasing the risk of DPN. Steiger directionality tests indicated that the causal relationships between circulating plasma proteins and DPN were consistent with expected directions. Conclusion This study identified 96 circulating plasma proteins with genetically determined levels that affect the risk of DPN, providing new potential targets for DPN drug development, particularly ITM2B, CREG1, CD14, and PLXNA4. |
| format | Article |
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| institution | OA Journals |
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| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-8e8418a7aee8496c80edcd838b0eaa062025-08-20T02:20:41ZengBMCCell & Bioscience2045-37012024-12-011411810.1186/s13578-024-01323-4Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysisXiaokun Chen0Guohua Jiang1Tianjing Zhao2Nian Sun3Shanshan Liu4Hao Guo5Canjun Zeng6Yijun Liu7Department of Orthopaedic Surgery, Shanghai Ninth People’s HospitalDepartment of Foot and Ankle Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Foot and Ankle Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Foot and Ankle Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical UniversityZhujiang Hospital of Southern Medical UniversityDepartment of Foot and Ankle Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Foot and Ankle Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical UniversityDepartment of Foot and Ankle Surgery, Center for Orthopedic Surgery, The Third Affiliated Hospital of Southern Medical UniversityAbstract Background Diabetic polyneuropathy (DPN) is a common diabetes complication with limited treatment options. We aimed to identify circulating plasma proteins as potential therapeutic targets for DPN using Mendelian Randomization (MR). Methods The protein quantitative trait loci (pQTLs) utilized in this study were derived from seven previously published genome-wide association studies (GWASs) on plasma proteomics. The DPN data were obtained from the IEU OpenGWAS project. This study employed two-sample MR using MR-Egger and inverse-variance weighted methods to evaluate the causal relationship between plasma proteins and DPN risk, with Cochran’s Q test, and I2 statistics, among other methods, used to validate the robustness of the results. Results Using cis-pQTLs as genetic instruments, we identified 62 proteins associated with DPN, with 33 increasing the risk and 29 decreasing the risk of DPN. Using cis-pQTLs + trans-pQTLs, we identified 116 proteins associated with DPN, with 44 increasing the risk and 72 decreasing the risk of DPN. Steiger directionality tests indicated that the causal relationships between circulating plasma proteins and DPN were consistent with expected directions. Conclusion This study identified 96 circulating plasma proteins with genetically determined levels that affect the risk of DPN, providing new potential targets for DPN drug development, particularly ITM2B, CREG1, CD14, and PLXNA4.https://doi.org/10.1186/s13578-024-01323-4Diabetic polyneuropathyComplications-nervesProteomicsMendelian randomizationDrug development |
| spellingShingle | Xiaokun Chen Guohua Jiang Tianjing Zhao Nian Sun Shanshan Liu Hao Guo Canjun Zeng Yijun Liu Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis Cell & Bioscience Diabetic polyneuropathy Complications-nerves Proteomics Mendelian randomization Drug development |
| title | Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis |
| title_full | Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis |
| title_fullStr | Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis |
| title_full_unstemmed | Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis |
| title_short | Identification of potential drug targets for diabetic polyneuropathy through Mendelian randomization analysis |
| title_sort | identification of potential drug targets for diabetic polyneuropathy through mendelian randomization analysis |
| topic | Diabetic polyneuropathy Complications-nerves Proteomics Mendelian randomization Drug development |
| url | https://doi.org/10.1186/s13578-024-01323-4 |
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