INTRODUCTION Several observational studies have indicated that polyunsaturated fatty acids serum levels (PUFAs) are associated with vascular dementia (VaD), but their causal relationships remain elusive. Therefore, we attempted to evaluate the causal effect of PUFAs on VaD in a two-sample Mendelian randomization (MR) analysis by using summary statistics from aggregated genome-wide association studies. METHODS The inverse-variance weighted (IVW) method was performed as the primary analysis. Sensitivity analyses (MR-Egger regression, weighted median, penalized weighted median and MR pleiotropy residual sum and outlier methods) were also implemented to estimate the effects of potential violations of MR hypotheses. RESULTS No causality was found for PUFAs (OR, 1.14; 95% CI, .91-1.42; p = .25) on VaD in the IVW model. The results were consistent in sensitivity analyses. There was no notable horizontal pleiotropy or heterogeneity. CONCLUSION In this two-sample MR analysis, our findings did not support the assumption that PUFAs play causal role in the occurrence or development of VaD.

中文翻译：

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多不饱和脂肪酸血清水平对血管性痴呆的影响：两样本孟德尔随机化研究。

引言 几项观察性研究表明，多不饱和脂肪酸血清水平（PUFA）与血管性痴呆（VaD）相关，但其因果关系仍然难以捉摸。因此，我们试图通过使用聚合全基因组关联研究的汇总统计数据，在两个样本孟德尔随机化 (MR) 分析中评估 PUFA 对 VaD 的因果影响。方法采用逆方差加权（IVW）法作为主要分析。还实施了敏感性分析（MR-Egger 回归、加权中值、惩罚加权中值和 MR 多效性残差和以及异常值方法）来估计潜在违反 MR 假设的影响。结果 IVW 模型中未发现 PUFA 与 VaD 存在因果关系（OR，1.14；95% CI，0.91-1.42；p = 0.25）。敏感性分析的结果是一致的。不存在显着的水平多效性或异质性。结论 在这个两个样本的 MR 分析中，我们的研究结果并不支持 PUFA 在 VaD 的发生或发展中起因果作用的假设。