基因证据表明磷脂酰胆碱是ω-3与多发性骨髓瘤风险之间因果关系的介质。
Genetic evidence reveals phosphatidylcholine as a mediator in the causal relationship between omega-3 and multiple myeloma risk.
作者信息
Li Jian, Li Youxuan, Wang Jun, Zhou Yilang, Wu Zhenzhen, Song Yu, Zhu Guoqing, Tian Jie
机构信息
The First College of Clinical Medicine, Guizhou University of Traditional Chinese Medicine, No. 71, Baoshan North Road, Yunyan District, Guiyang, 550001, Guizhou Province, China.
Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou Province, China.
出版信息
Sci Rep. 2025 Aug 8;15(1):29016. doi: 10.1038/s41598-025-12804-y.
Previous observational studies have indicated that omega-3 may reduce the risk of various cancers. However, the relationship between omega-3 and the incidence of multiple myeloma (MM) remains unclear. Therefore, we conducted a systematic Mendelian randomization (MR) analysis to investigate the causal relationship between omega-3 and the risk of developing MM, while also exploring the potential mediating role of plasma lipids in this association. First, we conducted a two-sample MR study with MM using the omega-3 GWAS data from Richardson TG. We then repeated the validation with the other three omega-3 GWAS data and performed a meta-analysis of the MR results for a total of four omega-3 data. In the second step, we used multivariate Mendelian randomization (MVMR) analyses to adjust for the effects of confounders and explore the direct causal effects of omega-3 with MM. In the third step, we employed a two-step MR to investigate the potential mediating roles of 179 plasma lipids in the association between omega-3 and the risk of MM. Multiple sensitivity analyses were used to assess the robustness of the results. A two-sample MR analysis found that omega-3 can reduce the risk of MM (OR = 0.80, 95% CI 0.69-0.94; P = 0.005). In subsequent validation, omega-3 data from both Kettunen J and Davyson E yielded similar results. However, data from Zhang S indicated that omega-3 was not associated with MM risk. Ultimately, the meta-analysis results demonstrated that omega-3 can lower the risk of MM (OR = 0.80, 95% CI 0.72-0.88; P < 0.001). Furthermore, MVMR analysis, after adjusting for relevant risk factors such as obesity and type 2 diabetes, confirmed that omega-3 still reduces the risk of MM. Finally, two-step MR identified phosphatidylcholine (18:2_20:4) as a potential mediator of the causal relationship between omega-3 and MM. Various sensitivity analyses validated the robustness of these findings. Our study suggests that omega-3 may reduce the incidence risk of MM by increasing the levels of phosphatidylcholine (18:2_20:4). We hope that these findings will provide new insights for the prevention and treatment of MM.
以往的观察性研究表明，ω-3可能降低多种癌症的风险。然而，ω-3与多发性骨髓瘤（MM）发病率之间的关系仍不明确。因此，我们进行了一项系统的孟德尔随机化（MR）分析，以研究ω-3与MM发病风险之间的因果关系，同时探讨血浆脂质在这种关联中的潜在中介作用。首先，我们使用来自Richardson TG的ω-3全基因组关联研究（GWAS）数据，对MM进行了两样本MR研究。然后，我们用其他三个ω-3 GWAS数据重复了验证，并对总共四个ω-3数据的MR结果进行了荟萃分析。在第二步中，我们使用多变量孟德尔随机化（MVMR）分析来调整混杂因素的影响，并探讨ω-3与MM之间的直接因果效应。在第三步中，我们采用两步MR来研究179种血浆脂质在ω-3与MM风险关联中的潜在中介作用。使用多种敏感性分析来评估结果的稳健性。两样本MR分析发现，ω-3可降低MM风险（比值比[OR]=0.80，95%置信区间[CI]0.69-0.94；P=0.005）。在随后的验证中，来自Kettunen J和Davyson E的ω-3数据产生了相似的结果。然而，来自Zhang S的数据表明，ω-3与MM风险无关。最终，荟萃分析结果表明，ω-3可降低MM风险（OR=0.80，95%CI 0.72-0.88；P<0.001）。此外，在调整了肥胖和2型糖尿病等相关风险因素后，MVMR分析证实ω-3仍可降低MM风险。最后，两步MR确定磷脂酰胆碱（18:2_20:4）是ω-3与MM因果关系的潜在中介。各种敏感性分析验证了这些发现的稳健性。我们的研究表明，ω-3可能通过提高磷脂酰胆碱（18:2_20:4）水平来降低MM的发病风险。我们希望这些发现将为MM的预防和治疗提供新的见解。
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