Department of Anesthesiology, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China.
Department of Joint Surgery, HongHui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi 710054, China.
J Affect Disord. 2023 Oct 1;338:69-73. doi: 10.1016/j.jad.2023.05.046. Epub 2023 May 25.
Major depression (MD) is a well-recognized risk factor for delirium. However, observational studies cannot provide direct evidence of causality between MD and delirium.
This study explored the genetic causal association between MD and delirium using two-sample Mendelian randomization (MR). Genome-wide association study (GWAS) summary data for MD were obtained from the UK Biobank. GWAS summary data for delirium were obtained from the FinnGen Consortium. Inverse-variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode were used to perform the MR analysis. In addition, the Cochrane's Q test was used to detect heterogeneity in the MR results. Horizontal pleiotropy was detected using the MR-Egger intercept test and MR pleiotropy residual sum and outliers (MR-PRESSO) test. Leave-one-out analysis was used to investigate the sensitivity of this association.
The IVW method showed that MD was an independent risk factor for delirium (P = 0.013). Horizontal pleiotropy was unlikely to bias causality (P > 0.05), and no evidence of heterogeneity was found between the genetic variants (P > 0.05). Finally, a leave-one-out test showed that this association was stable and robust.
All participants included in the GWAS were of European ancestry. Due to database limitations, the MR analysis did not conduct stratified analyses for different countries, ethnicities, or age groups.
We conducted a two-sample MR analysis and found the evidence of genetic causal association between MD and delirium.
重度抑郁症（MD）是谵妄的公认危险因素。然而，观察性研究不能提供 MD 和谵妄之间因果关系的直接证据。
本研究使用两样本 Mendelian 随机化（MR）探索 MD 和谵妄之间的遗传因果关联。MD 的全基因组关联研究（GWAS）汇总数据从英国生物库获得。谵妄的 GWAS 汇总数据从芬兰遗传（FinnGen）联盟获得。采用逆方差加权（IVW）、MR Egger、加权中位数、简单模式和加权模式进行 MR 分析。此外，还使用 Cochrane's Q 检验检测 MR 结果中的异质性。使用 MR-Egger 截距检验和 MR 多效性残差和异常值（MR-PRESSO）检验检测水平多效性。采用逐一删除分析来调查该关联的敏感性。
IVW 方法表明 MD 是谵妄的独立危险因素（P=0.013）。水平多效性不太可能导致因果关系偏倚（P>0.05），并且遗传变异之间没有发现异质性（P>0.05）。最后，逐一删除测试表明该关联是稳定和可靠的。
所有纳入 GWAS 的参与者均为欧洲血统。由于数据库的限制，MR 分析未对不同国家、种族或年龄组进行分层分析。
我们进行了两样本 MR 分析，发现 MD 和谵妄之间存在遗传因果关联的证据。
