Causal Associations Between Sleep Traits and Delirium: A Bidirectional Two-Sample Mendelian Randomization Study

Hao Liu,1,2,* Zhengze Zhang,1,2,* Yuewen He,1,2 Longfei Ding,1,2 Tong Wu,1,2 Yong Wang,2,3 Wuhua Ma2 1Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China; 3State Key Laboratory of Traditional Chinese Medicine Syndrome, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wuhua Ma; Yong Wang, Department of Anesthesiology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, 16 Jichang Road, Guangzhou, Guangdong, 510405, People’s Republic of China, Tel +86 13318860680 ; +86 15920382796, Email [email protected]; [email protected]: Numerous studies have identified a correlation between sleep and delirium; however, the causal relationship remains ambiguous. This bidirectional two-sample Mendelian randomization (MR) study was conducted to examine the possible causal relationships between sleep traits and delirium.Patients and Methods: Utilizing genome-wide association studies (GWAS), we identified ten sleep traits: chronotype, sleep duration, short sleep duration, long sleep duration, daytime napping, daytime sleepiness, insomnia, number of sleep episodes (NSE), sleep efficiency, and rapid eye movement sleep behavior disorder (RBD). In this MR study, genetic variants independently associated with exposures were selected as instrumental variables (IVs). To establish causal inferences, three regression models were employed—inverse variance weighted (IVW), MR Egger, and weighted median (WM) —and conducted sensitivity analyses to assess the robustness of our findings.Results: Our results suggest no significant causal association between the ten sleep traits and the risk of delirium. The reverse MR analysis revealed that delirium is associated with an increased propensity for morning chronotype [ORIVW, 1.025; 95% CI, 1.012– 1.036; p = 1.50E-05; adjusted p values (padjusted)= 1.35E-04] and a decreased risk of long sleep duration [ORIVW, 0.996; 95% CI, 0.993– 0.999; p = 0.013; padjusted= 0.059]. However, no robust evidence currently exists to substantiate a causal relationship between delirium and other sleep traits.Conclusion: Our bidirectional, two-sample MR analysis study did not provide definitive evidence that sleep traits may augment the susceptibility to delirium. However, the reverse MR results indicate that delirium may predispose patients to an earlier sleep-wake cycle. Additional large-scale investigations are necessary to examine the bidirectional causality between delirium and sleep traits.Keywords: sleep traits, delirium, Mendelian randomization analysis, genome-wide association studies