Wan Xianjie, Yu Hui, Yang Mingyi, Hou Weikun, Xie Jiale, Xu Ke, Ma Yujie, Ma Rui, Wang Fan, Xu Peng
Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710054, China.
Heliyon. 2024 Mar 23;10(7):e28697. doi: 10.1016/j.heliyon.2024.e28697. eCollection 2024 Apr 15.
This study aimed to investigate whether there is a causal relationship between educational attainment and delirium at the genetic level using the Mendelian randomization method, and provide new evidence for studies in this field. We found a causal relationship between educational attainment and delirium at the genetic level after excluding confounders using Mendelian randomization. The inverse variance weighting method of random effects was the main analysis method. The weighted median and Mendelian Randomization-Egger methods, as well as simple, and weighted modes were used as supplementary analysis methods. Additionally, horizontal pleiotropy tests were conducted, including the Mendelian Randomization-Egger intercept test and Mendelian Randomization Pleiotropy RESidual Sum and Outlier. Cochran's Q statistic was used to assess the size of heterogeneity. We retrieved all second single nucleotide polymorphism features and performed multivariate Mendelian randomization to adjust for the effect of potential confounders on our results. The inverse variance weighting suggested a negative correlation between genetically predicted educational attainment and delirium (0.67[0.49-0.92], p = 0.013); Mendelian Randomization Pleiotropy RESidual Sum and Outlier (0.67[0.49-0.92], p = 0.013) and multivariate Mendelian randomization (0.52[0.33-0.82], p = 0.005) results were generally consistent with the inverse variance weighting method. The Mendelian Randomization-Egger, simple, and weighted mode results were consistent with the inverse variance weighting results. Our results were not affected by pleiotropy or heterogeneity (p > 0.05, for both pleiotropy and heterogeneity). In addition, the "leave-one-out" analysis showed that the results of our Mendelian randomization analysis were not influenced by individual single nucleotide polymorphisms. Studies have found a causal relationship between educational attainment and delirium at the genetic level; higher educational attainment may be a protective factor against delirium. Clinically, more attention should be paid to patients at a high risk of delirium with low educational attainment.
本研究旨在使用孟德尔随机化方法在基因水平上探究教育程度与谵妄之间是否存在因果关系,并为该领域的研究提供新证据。我们通过孟德尔随机化排除混杂因素后,发现在基因水平上教育程度与谵妄之间存在因果关系。随机效应的逆方差加权法是主要分析方法。加权中位数和孟德尔随机化-埃格法以及简单和加权模式用作补充分析方法。此外,还进行了水平多效性检验,包括孟德尔随机化-埃格截距检验和孟德尔随机化多效性残差和异常值检验。 Cochr an's Q统计量用于评估异质性大小。我们检索了所有第二代单核苷酸多态性特征,并进行多变量孟德尔随机化以调整潜在混杂因素对我们结果的影响。逆方差加权表明基因预测的教育程度与谵妄之间存在负相关(0.67[0.49 - 0.92],p = 0.013);孟德尔随机化多效性残差和异常值检验(0.67[0.49 - 0.92],p = 0.013)和多变量孟德尔随机化(0.52[0.33 - 0.82],p = 0.005)结果与逆方差加权法总体一致。孟德尔随机化-埃格法、简单和加权模式结果与逆方差加权结果一致。我们的结果不受多效性或异质性影响(多效性和异质性的p均>0.05)。此外,“留一法”分析表明我们的孟德尔随机化分析结果不受单个单核苷酸多态性影响。研究发现在基因水平上教育程度与谵妄之间存在因果关系;较高的教育程度可能是预防谵妄的保护因素。临床上,应更加关注教育程度低且有谵妄高风险的患者。