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Identification of Gene Loci That Overlap Between Mental Disorders and Poor Prognosis of Cancers.

ABSTRACT: Background: Co-morbid psychiatric disorders are common in patients with cancers, which make the treatment more difficult. Studying the connection between mental disease-related genes and the prognosis of cancers may potentially lead to novel therapeutic methods. Method: All mental disorders genes were selected from published articles. The correlations between the expression of these genes and the prognosis of different cancers were analyzed by starBase v2.0 and TIMER. The molecular functions, reactome pathways, and interactions among diverse genes were explored via the STRING tool. Results: 239 genes were identified for further survival analysis, 5 of which were overlapping genes across at least five cancer types, including RHEBL1, PDE4B, ANKRD55, EPHB2, and GIMAP7. 146 high-expression and 157 low-expression genes were found to be correlated with the unfavorable prognosis of diverse cancer types. Tight links existed among various mental disease genes. Besides, risk genes were mostly related to the dismal outcome of low-grade glioma (LGG) and kidney renal clear cell carcinoma (KIRC) patients. Gene Ontology (GO) and reactome pathway analysis revealed that most genes involved in various critical molecular functions and primarily related to metabolism, signal transduction, and hemostasis. Conclusions: To explore co-expression genes between mental illnesses and cancers may aid in finding preventive strategies and therapeutic methods for high-risk populations and patients with one or more diseases.

SUBMITTER: Xu JL

PROVIDER: S-EPMC8273260 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Psychiatric disorders and common epilepsies are heritable disorders with a high comorbidity and overlapping symptoms. However, the causative mechanisms underlying this relationship are poorly understood. Here we aimed to identify overlapping genetic loci between epilepsy and psychiatric disorders to gain a better understanding of their comorbidity and shared clinical features. We analysed genome-wide association study data for all epilepsies (n = 44 889), genetic generalized epilepsy (n = 33 446), focal epilepsy (n = 39 348), schizophrenia (n = 77 096), bipolar disorder (n = 406 405), depression (n = 500 199), attention deficit hyperactivity disorder (n = 53 293) and autism spectrum disorder (n = 46 350). First, we applied the MiXeR tool to estimate the total number of causal variants influencing the disorders. Next, we used the conjunctional false discovery rate statistical framework to improve power to discover shared genomic loci. Additionally, we assessed the validity of the findings in independent cohorts, and functionally characterized the identified loci. The epilepsy phenotypes were considerably less polygenic (1.0 K to 3.4 K causal variants) than the psychiatric disorders (5.6 K to 13.9 K causal variants), with focal epilepsy being the least polygenic (1.0 K variants), and depression having the highest polygenicity (13.9 K variants). We observed cross-trait genetic enrichment between genetic generalized epilepsy and all psychiatric disorders and between all epilepsies and schizophrenia and depression. Using conjunctional false discovery rate analysis, we identified 40 distinct loci jointly associated with epilepsies and psychiatric disorders at conjunctional false discovery rate <0.05, four of which were associated with all epilepsies and 39 with genetic generalized epilepsy. Most epilepsy risk loci were shared with schizophrenia (n = 31). Among the identified loci, 32 were novel for genetic generalized epilepsy, and two were novel for all epilepsies. There was a mixture of concordant and discordant allelic effects in the shared loci. The sign concordance of the identified variants was highly consistent between the discovery and independent datasets for all disorders, supporting the validity of the findings. Gene-set analysis for the shared loci between schizophrenia and genetic generalized epilepsy implicated biological processes related to cell cycle regulation, protein phosphatase activity, and membrane and vesicle function; the gene-set analyses for the other loci were underpowered. The extensive genetic overlap with mixed effect directions between psychiatric disorders and common epilepsies demonstrates a complex genetic relationship between these disorders, in line with their bi-directional relationship, and indicates that overlapping genetic risk may contribute to shared pathophysiological and clinical features between epilepsy and psychiatric disorders.

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Identification of Gene Loci That Overlap Between Mental Disorders and Poor Prognosis of Cancers.

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