■多发性骨髓瘤(MM),起源于骨髓的浆细胞的恶性疾病,受遗传因素的影响很大。虽然血浆脂质体已经与MM有关,他们潜在的因果关系的性质还有待阐明。本研究旨在使用孟德尔随机化(MR)分析来探索这种关系。
■在全基因组关联研究(GWAS)汇集数据库中,从7,174名芬兰个体的血浆脂质组学数据中鉴定了脂质体相关的遗传工具变量(IVs)。MM汇集的数据集来自GWAS荟萃分析,包括150,797名个体,包括598名MM患者和218,194名对照。这些静脉注射进行了MR分析,坚持严格的相关性标准,独立性,以及排除混杂因素。逆方差加权(IVW)方法,MR-Egger方法,加权中位数(WM)法,和简单中位数用于MR分析评估,在Cochran的Q测试旁边,MR-Egger截获,MR-Pleiotropy残差和离群值(MR-RESSO)方法,和用于评估异质性的留一法分析,多重性,和工具偏见。
■该研究确定了88个有意义的,独立的单核苷酸多态性(SNP)作为MR分析的IVs,每个都有一个大于10的F统计值,表明对弱仪器偏差的鲁棒性。IVW分析显示六种血浆脂质体成分与MM风险之间存在关联(p<0.05)。磷脂酰肌醇(16:0_18:1)血清水平(比值比[OR]=1.769,95%置信区间[CI]:1.132-2.763,p=0.012)和三酰甘油(56:4)水平(p=0.026,OR=1.417,95%CI:1.042-1.926)与多发性骨髓瘤的发展风险呈正相关。磷脂酰乙醇胺(18:0_20:4)(p=0.004,95%CI:0.621-0.916,OR=0.754),磷脂酰胆碱(18:2_20:4)(p=0.004,OR=0.680,95%CI:0.519-0.889),甾醇酯(27:1/18:3)水平(p=0.013,OR=0.677,95%CI:0.498-0.922),和磷脂酰胆碱(O-18:2_20:4)水平(OR=0.710,95%CI:0.517-0.913,p=0.033)与发生多发性骨髓瘤的风险呈负相关。Cochran的Q检验没有检测到统计方法的异质性,MR-RESSO检验或MR-Egger截距也未检测到水平多效性;留一法分析证实了个体SNP不存在偏倚.
■我们的发现表明血浆脂质体成分与MM风险之间存在复杂的关系。血清三酰甘油和磷脂酰肌醇水平升高与MM风险呈正相关。而某些磷脂和甾醇酯提供保护作用。这项研究为脂质体在多发性骨髓瘤病理中的临床相关性提供了有价值的见解。
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.