BACKGROUND: Numerous studies have identified a correlation between sleep disorders and delirium; however, the causal relationship remains ambiguous. This bidirectional two-sample Mendelian randomization (MR) study, combined with colocalization and enrichment analyses, aims to investigate the potential causal relationship between sleep-associated phenotypes and delirium.
METHODS: We performed a two-sample bidirectional Mendelian randomization analysis using 10 gene variants associated with sleep phenotypes to investigate the causal relationship between sleep disorders and delirium. Five methods for MR Analysis. Moreover, sensitivity analyses were conducted to assess the robustness of our findings. Enrichment and colocalization analyses were conducted to uncover the genetic mechanisms linking sleep phenotypes and delirium.
RESULTS: The IVW method showed that insomnia positively correlates with delirium (OR = 2.523, 95 % CI: 1.048-6.079, P = 0.039). Morning person is causally negatively associated with delirium (OR = 0.869, 95 % CI: 0.774-0.977, P = 0.018). Conversely, delirium is negatively associated with daytime napping (OR = 0.987, 95 % CI: 0.984-0.990, P < 0.001), insomnia (OR = 0.985, 95 % CI: 0.981-0.989, P < 0.001), snoring (OR = 0.991, 95 % CI: 0.985-0.997, P = 0.002), and single item chronotype (beta = -0.161, 95 % CI:0.241-0.081, P = 0.002). Insomnia-related genes are enriched in neuro-metabolic and epigenetic pathways, while Morning person is linked to circadian rhythm regulation. A morning person shares genetic signals with delirium at the rs2398144 locus on chromosome 16 (PPH4 > 0.5).
CONCLUSIONS: Our findings provide evidence for a potential causal relationship between sleep disorders and delirium.These findings may support better prevention and management of delirium in older adults.
