Identification of key genes and immune infiltration modulated in insomnia by integrated bioinformatics analysis and mendelian randomization study

Abstract

Insomnia is a prevalent sleep disorder in modern times, often linked to various factors. Its occurrence, in turn, can lead to the development of several diseases, such as common cardiovascular conditions like coronary heart disease and hypertension. Moreover, insomnia can significantly impact the strength of the immune system. Traditional Chinese medicine (TCM) classifies sleep deprivation as a form of sleepiness, attributing prolonged sleepiness to Yin-Yang imbalance, resulting in Qi consumption and impairment of the five Zang-organs. Both Qi consumption and damage to the five Zang-organs mentioned in TCM research are correlated with the immune system in medical studies. Consequently, current research indicates that sleep deprivation escalates the risk of immune-related diseases. However, more research and analysis concerning immune infiltration related explicitly to insomnia are needed. Through gene differential analysis of sample files obtained from the Gene Expression Omnibus (GEO) dataset GSE208668 , we identified differentially expressed genes (DEGs) between the Insomnia and control groups. After screening these DEGs, we conducted GO and KEGG pathway analyses to identify insomnia-related gene pathways. Subsequently, I identified ten hub genes (IL2, CALML3, GATA3, EOMES, PTGS2, ESCO2, CXCL2, GPT, CRT, PRF1), and using a logistic regression model, I predicted insomnia based on the expression patterns of these ten genes. The analysis revealed that CALML3 and IL2, which showed the best performance in ROC curve analysis and had the highest degree, respectively, were selected for further investigation. Continuing the research, we further employed CIBERSORT to study immune infiltration in patients with insomnia, discovering an association between mast cells and insomnia partially correlated with the identified hub genes. In conclusion, these essential genes and immune infiltrations are relevant for treating and alleviating insomnia. Understanding these genes and immune cells could offer crucial insights for future therapeutic approaches to insomnia.