Scholarlink

<p>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; <i>P</i> = 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; <i>P</i> &lt; 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.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Genetic evidence reveals phosphatidylcholine as a mediator in the causal relationship between omega-3 and multiple myeloma risk

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年8月8日

查看全文
  • Jian Li,
  • Youxuan Li,
  • Jun Wang,
  • Yilang Zhou,
  • Zhenzhen Wu,
  • Yu Song,
  • Guoqing Zhu,
  • Jie Tian

摘要

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.