Impact of psychiatric disorders on the risk of glioma: Mendelian randomization and biological annotation

Background: The conflicting results about the relationship between certain psychiatric disorders and glioma has been reported in previous studies. Moreover, little is known about the common pathogenic mechanism between psychiatric symptoms and glioma. This study aims to find out mental disorders related etiology of glioma and to interpret the underlying biological mechanisms. Methods: A panel of SNPs significantly associated with eight psychiatric disorders (ADHD, SCZ, Insomnia, NEU, MDD, MI, BIP, and SWB) were identified as exposure related genetic instruments. Summary GWAS data for glioma comes from eight independent datasets. Two sample Mendelian randomization study was undertaken by IVW, RAPS, MR.Corr, and BWMR methods. This study incorporated the glioma associated CGGA cohort and Rembrandt cohort. ssGSEA, variance expression, and KEGG were conducted to analyze the psychiatric disorders associated genes expression profiling and associated functional enrichment in the glioma patients. Results: ADHD has a suggestive risk effect on all glioma (OR = 1.15, 95%CI = 1.01--1.29, P = 0.028) and a significant causal effect on non-GBM glioma (OR = 1.33, 95%CI = 1.12--1.58, P = 0.001). Similarly, SCZ displayed a causal relationship with all glioma (OR = 1.09, 95%CI = 1.04-1.14, P = 3.47 x 10(-4)) and non-GBM glioma (OR = 1.14, 95%CI = 1.08-1.21, P = 7.37 x 10(-6)). Besides, insomnia was correlated with the risk of non-GBM glioma (OR = 1.49, 95%CI = 1.03-2.17, P = 0.036). The ADHD/SCZ/Insomnia associated DEGs of glioma patients were enriched in neurotransmitter signaling pathway, immune reaction, adhesion, invasion, and metastasis, regulating the pluripotency of stem cells, metabolism of glycan, lipid and amino acids. Limitations: The extensibility of the conclusion to other ethnic and geographical groups should be careful because the data used in this study come from European. Conclusions: This study provides genetic evidence to suggest ADHD, SCZ, and insomnia as causes of glioma and common pathogenic process between ADHD/Insomnia/SCZ and glioma.