Causal role of plasma liposome in diabetic retinopathy: mendelian randomization (MR) study
Kai Yin1, Lu Ding2,3, Xueyan Li1
1College of Integrated Traditional Chinese and Western Medicine, Changchun University of Chinese Medicine, Changchun, Jilin, 130117, China.
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), Pfdr = 0.006], phosphatidylcholine (16:0_20:2) levels [OR = 0.893 (0.834 to 0.956), Pfdr = 0.043] and phosphatidylethanolamine (18:0_20:4) levels [OR = 0.906 (0.863 to 0.951), Pfdr = 0.006] were protective against DR, whereas sphingomyelin (d36:1) levels [OR = 1.120 (1.061 to 1.183), Pfdr = 0.006], and sphingomyelin (d40:1) levels [OR = 1.081 (1.031 to 1.134), Pfdr = 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.
Insights
Genetic analysis reveals specific lipid levels causally influence diabetic retinopathy (DR) risk. Lower levels of certain phosphatidylcholines and phosphatidylethanolamines protect against DR, while higher sphingomyelins increase risk.
Area of Science:
- Metabolomics and Genetics
- Ophthalmology
- Endocrinology
Background:
- Observational studies suggest a link between plasma lipidome and diabetic retinopathy (DR) incidence.
- The causal nature of this association requires rigorous investigation.
Purpose of the Study:
- To employ a two-sample Mendelian randomization (MR) analysis to determine the causal relationship between lipidome levels and DR.
- To assess the impact of specific lipid metabolites on DR risk.
Main Methods:
- Utilized summary statistics from GWAS Catalog and FinnGen Consortium for lipid levels and DR.
- Performed two-sample MR analysis using inverse variance weighted (IVW), MR-Egger, and weighted median methods.
- Assessed for heterogeneity and horizontal pleiotropy using Cochran's Q, MR-PRESSO, and MR-Egger regression.
Main Results:
- Five lipid levels showed a significant association with DR risk after FDR correction.
- Phosphatidylcholine (16:0_16:0), phosphatidylcholine (16:0_20:2), and phosphatidylethanolamine (18:0_20:4) were protective against DR.
- Sphingomyelin (d36:1) and sphingomyelin (d40:1) levels were associated with an increased risk of DR.
Conclusions:
- Genetic evidence supports a causal link between specific lipid levels and DR.
- Findings offer insights into lipid metabolism's role in DR pathogenesis.
- Results may guide future strategies for DR prevention and treatment.
