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Liposomes have a direct effect on multiple myeloma: a Mendelian randomization study
Yingbin Zhong1,2,3,4, Yanhao Li1, Weipeng Sun5
1Guangzhou University of Chinese Medicine, Guangzhou, China.
Background:
Multiple myeloma (MM), a malignant disease of plasma cells originating in the bone marrow, is influenced significantly by genetic factors. Although plasma liposomes have been linked to MM, the nature of their potential causal relationship remains to be elucidated. This study aims to explore this relationship using Mendelian randomization (MR) analysis.
Methods:
Liposome-associated genetic instrumental variables (IVs) were identified from plasma lipidomics data of 7,174 Finnish individuals within a Genome-Wide Association Study (GWAS) pooled database. A MM pooled dataset was sourced from a GWAS meta-analysis encompassing 150,797 individuals, including 598 MM patients and 218,194 controls. These IVs underwent MR analysis, adhering to strict criteria for correlation, independence, and the exclusion of confounders. The inverse variance weighted (IVW) method, MR-Egger method, weighted median (WM) method, and simple median were utilized for MR analysis assessment, alongside Cochran's Q test, MR-Egger intercept, MR-Pleiotropy Residual Sum and Outlier (MR-RESSO) method, and leave-one-out analysis for evaluating heterogeneity, multiplicity, and instrumental bias.
Results:
The study identified 88 significant, independent single nucleotide polymorphisms (SNPs) as IVs for MR analysis, each with an F-statistic value above 10, indicating robustness against weak instrument bias. IVW analysis revealed associations between six plasma liposome components and MM risk (p < 0.05). Phosphatidylinositol (16:0_18:1) serum levels (odds ratio [OR] = 1.769, 95% confidence interval [CI]: 1.132-2.763, p = 0.012) and triacylglycerol (56:4) levels (p = 0.026, OR = 1.417, 95% CI: 1.042-1.926) were positively correlated with the risk of multiple myeloma development. Phosphatidylethanolamine (18:0_20:4) (p = 0.004, 95% CI: 0.621-0.916, OR = 0.754), phosphatidylcholine (18:2_20:4) (p = 0.004, OR = 0.680, 95% CI: 0.519-0.889), sterol ester (27:1/18:3) levels (p = 0.013, OR = 0.677, 95% CI: 0.498-0.922), and phosphatidylcholine (O-18:2_20:4) levels (OR = 0.710, 95% CI: 0.517-0.913, p = 0.033) were negatively associated with the risk of developing multiple myeloma. The Cochran's Q test did not detect statistical method heterogeneity, nor did the MR-RESSO test or the MR-Egger intercept detect horizontal pleiotropy; leave-one-out analyses confirmed the absence of bias from individual SNPs.
Conclusions:
Our findings suggest a complex relationship between plasma liposome components and MM risk. Elevated serum levels of triacylglycerol and phosphatidylinositol are positively associated with MM risk, while certain phospholipids and sterol esters offer a protective effect. This study provides valuable insights into the clinical relevance of liposomes in the pathology of multiple myeloma.
Insights
This study used Mendelian randomization to investigate the link between plasma lipids and multiple myeloma (MM). Certain lipids like triacylglycerol increase MM risk, while others, such as phospholipids, may offer protection.
Area of Science:
- Genetics
- Biochemistry
- Oncology
Background:
- Multiple myeloma (MM) is a plasma cell malignancy influenced by genetic factors.
- The role of plasma liposomes in MM etiology requires further elucidation.
- This study investigates the causal relationship between plasma liposomes and MM risk.
Purpose of the Study:
- To explore the potential causal relationship between plasma liposome components and multiple myeloma (MM) risk.
- To utilize Mendelian randomization (MR) analysis for robust genetic association.
- To identify specific lipid biomarkers associated with MM development.
Main Methods:
- Mendelian randomization (MR) analysis was performed using genetic instrumental variables (IVs) from plasma lipidomics data.
- A large pooled dataset from Genome-Wide Association Studies (GWAS) for MM was utilized.
- Multiple MR methods and sensitivity analyses were employed to ensure validity and assess bias.
Main Results:
- 88 robust genetic instrumental variables (IVs) were identified for MR analysis.
- Six plasma liposome components showed significant associations with MM risk.
- Elevated triacylglycerol and phosphatidylinositol levels were positively associated with MM risk.
- Certain phospholipids and sterol esters demonstrated a negative association, suggesting a protective effect.
Conclusions:
- Plasma liposome components exhibit a complex relationship with multiple myeloma (MM) risk.
- Specific lipids like triacylglycerol and phosphatidylinositol may increase MM risk.
- Other lipids, including phospholipids and sterol esters, may confer a protective effect against MM.
