孟德尔随机化探究Omega-3脂肪酸与乳腺癌发病风险的因果关系

Causal Association Between Omega-3 Fatty Acids and Risk of Breast Cancer:A Mendelian Randomization Study

目的利用孟德尔随机化方法分析Omega-3脂肪酸与乳腺癌发病风险的因果关联。方法对Omega-3脂肪酸与乳腺癌全基因组关联研究(GWASs)数据进行分析,筛选出与Omega-3脂肪酸相关的遗传位点作为工具变量(IVs)。使用逆方差加权(IVW)、MR-Egger、加权中位数、简单模式和加权模式等孟德尔随机化分析方法对Omega-3脂肪酸和乳腺癌发病风险间的因果关系进行评估。结果共筛选出47个与Omega-3脂肪酸强相关的SNPs作为工具变量,IVW等分析方法均显示Omega-3脂肪酸与乳腺癌的发病风险间不存在因果关联(P>0.05)。MR-Egger回归分析等方法均未检测到明显的基因水平多效性(P=0.319),表明分析结果具有较高的敏感性和稳健性。结论Omega-3脂肪酸与乳腺癌发病风险之间无因果关联。

Objective To explore the causal relationship between Omega-3 fatty acids and the risk of breast cancer via Mendelian randomization analysis.Methods Analysis was conducted on data from genome-wide association studies(GWASs)on Omega-3 fatty acids and breast cancer.The selected instrumental variables(IVs)comprised genetic loci associated with Omega-3 fatty acids.Various Mendelian randomization analysis methods,including inverse-variance weighted(IVW)method,MR–Egger regression analysis,weighted median,simple models,and weighted models,were used to evaluate the causal relationship between Omega-3 fatty acids and the risk of breast cancer.Results A total of 47 single-nucleotide polymorphisms strongly associated with Omega-3 fatty acids were selected as IVs.The analysis methods,including IVW method,revealed no causal relationship between Omega-3 fatty acids and the risk of breast cancer(P>0.05).Analysis methods,such as MR-Egger regression analysis,did not detect significant gene-level pleiotropy(P=0.319),which indicates the high sensitivity and robustness of analysis results.Conclusion The findings of this study suggest the absence of a causal relationship between Omega-3 fatty acids and the risk of breast cancer.