Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study
Abstract Background Research indicates that there may be an association between plasma lipidome levels and the incidence of diabetic retinopathy (DR) in patients. However, the potential causality of this relationship is yet to be determined. To investigate this matter further, we employed a two-samp...
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BMC
2025-02-01
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| Series: | Diabetology & Metabolic Syndrome |
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| Online Access: | https://doi.org/10.1186/s13098-025-01612-z |
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| author | Kai Yin Lu Ding Xueyan Li Yuqi Zhang Siyu Song Liyuan Cao Ruixue Deng Min Li Zirui Li Qinjing Xia Daqing Zhao Xiangyan Li Zeyu Wang |
| author_facet | Kai Yin Lu Ding Xueyan Li Yuqi Zhang Siyu Song Liyuan Cao Ruixue Deng Min Li Zirui Li Qinjing Xia Daqing Zhao Xiangyan Li Zeyu Wang |
| author_sort | Kai Yin |
| collection | DOAJ |
| description | Abstract Background Research indicates that there may be an association between plasma lipidome levels and the incidence of diabetic retinopathy (DR) in patients. However, the potential causality of this relationship is yet to be determined. To investigate this matter further, we employed a two-sample Mendelian randomization (MR) analysis to comprehensively assess the causality between lipidome levels and DR. Methods Summary statistics for lipid levels and DR were obtained from the Genome-Wide Association Studies (GWAS) Catalog database and the FinnGen Consortium, respectively. We conducted a two-sample MR analysis, and statistical analysis were performed using the inverse variance weighted (IVW) with the addition of the MR-Egger, weighted median (WM), constrained maximum likelihood and model averaging (cML-MA) to test for causal associations between lipid levels and DR. Heterogeneity was checked using Cochran’s Q statistic. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) global test and the MR-Egger regression were used to detect horizontal pleiotropy. The robustness of our findings was assessed using leave-one-out and funnel plots. To further assess the reliability of the results, linkage disequilibrium score regressions, colocalization analysis and reverse MR analysis were also performed. Results Analysis of the pooled MR results and after correction for the false discovery rate (FDR) revealed that five lipid levels were associated with DR risk. Phosphatidylcholine (16:0_16:0) levels [OR = 0.869 (0.810 to 0.933), P fdr = 0.006], phosphatidylcholine (16:0_20:2) levels [OR = 0.893 (0.834 to 0.956), P fdr = 0.043] and phosphatidylethanolamine (18:0_20:4) levels [OR = 0.906 (0.863 to 0.951), P fdr = 0.006] were protective against DR, whereas sphingomyelin (d36:1) levels [OR = 1.120 (1.061 to 1.183), P fdr = 0.006], and sphingomyelin (d40:1) levels [OR = 1.081 (1.031 to 1.134), P fdr = 0.043] were associated with a greater risk of DR. Further sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy. Conclusion In summary, genetic evidence suggests a causal relationship between the levels of specific lipid levels and DR. These findings may provide valuable insights into the causal relationships between lipid levels and DR, potentially informing future prevention and treatment strategies. |
| format | Article |
| id | doaj-art-909f42de454f46ec8ccabbd38cf572ba |
| institution | Kabale University |
| issn | 1758-5996 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | BMC |
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| series | Diabetology & Metabolic Syndrome |
| spelling | doaj-art-909f42de454f46ec8ccabbd38cf572ba2025-02-09T12:48:15ZengBMCDiabetology & Metabolic Syndrome1758-59962025-02-0117111110.1186/s13098-025-01612-zCausal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) studyKai Yin0Lu Ding1Xueyan Li2Yuqi Zhang3Siyu Song4Liyuan Cao5Ruixue Deng6Min Li7Zirui Li8Qinjing Xia9Daqing Zhao10Xiangyan Li11Zeyu Wang12College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese MedicineResearch Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese MedicineCollege of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese MedicineThird Clinical Hospital, Changchun University of Chinese MedicineNortheast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese MedicineCollege of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese MedicineCollege of Traditional Chinese Medicine, Changchun University of Chinese MedicineCollege of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese MedicineCollege of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese MedicineCollege of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese MedicineNortheast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese MedicineNortheast Asia Research Institute of Traditional Chinese Medicine, Key Laboratory of Active Substances and Biological Mechanisms of Ginseng Efcacy, Ministry of Education, Jilin Provincial Key Laboratory of Bio-Macromolecules of Chinese Medicine, Changchun University of Chinese MedicineResearch Center of Traditional Chinese Medicine, The Affiliated Hospital to Changchun University of Chinese MedicineAbstract Background Research indicates that there may be an association between plasma lipidome levels and the incidence of diabetic retinopathy (DR) in patients. However, the potential causality of this relationship is yet to be determined. To investigate this matter further, we employed a two-sample Mendelian randomization (MR) analysis to comprehensively assess the causality between lipidome levels and DR. Methods Summary statistics for lipid levels and DR were obtained from the Genome-Wide Association Studies (GWAS) Catalog database and the FinnGen Consortium, respectively. We conducted a two-sample MR analysis, and statistical analysis were performed using the inverse variance weighted (IVW) with the addition of the MR-Egger, weighted median (WM), constrained maximum likelihood and model averaging (cML-MA) to test for causal associations between lipid levels and DR. Heterogeneity was checked using Cochran’s Q statistic. The MR Pleiotropy Residual Sum and Outlier (MR-PRESSO) global test and the MR-Egger regression were used to detect horizontal pleiotropy. The robustness of our findings was assessed using leave-one-out and funnel plots. To further assess the reliability of the results, linkage disequilibrium score regressions, colocalization analysis and reverse MR analysis were also performed. Results Analysis of the pooled MR results and after correction for the false discovery rate (FDR) revealed that five lipid levels were associated with DR risk. Phosphatidylcholine (16:0_16:0) levels [OR = 0.869 (0.810 to 0.933), P fdr = 0.006], phosphatidylcholine (16:0_20:2) levels [OR = 0.893 (0.834 to 0.956), P fdr = 0.043] and phosphatidylethanolamine (18:0_20:4) levels [OR = 0.906 (0.863 to 0.951), P fdr = 0.006] were protective against DR, whereas sphingomyelin (d36:1) levels [OR = 1.120 (1.061 to 1.183), P fdr = 0.006], and sphingomyelin (d40:1) levels [OR = 1.081 (1.031 to 1.134), P fdr = 0.043] were associated with a greater risk of DR. Further sensitivity analysis did not reveal heterogeneity or horizontal pleiotropy. Conclusion In summary, genetic evidence suggests a causal relationship between the levels of specific lipid levels and DR. These findings may provide valuable insights into the causal relationships between lipid levels and DR, potentially informing future prevention and treatment strategies.https://doi.org/10.1186/s13098-025-01612-zDiabetic retinopathyLipidMendelian randomizationGenome-wide association studyCausation |
| spellingShingle | Kai Yin Lu Ding Xueyan Li Yuqi Zhang Siyu Song Liyuan Cao Ruixue Deng Min Li Zirui Li Qinjing Xia Daqing Zhao Xiangyan Li Zeyu Wang Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study Diabetology & Metabolic Syndrome Diabetic retinopathy Lipid Mendelian randomization Genome-wide association study Causation |
| title | Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study |
| title_full | Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study |
| title_fullStr | Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study |
| title_full_unstemmed | Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study |
| title_short | Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study |
| title_sort | causal role of plasma liposome in diabetic retinopathy mendelian randomization mr study |
| topic | Diabetic retinopathy Lipid Mendelian randomization Genome-wide association study Causation |
| url | https://doi.org/10.1186/s13098-025-01612-z |
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