Gene expression overlap between neuropsychiatric disorders

Common diseases result from a mix of genetic and environmental factors, often involving inflammation. Complex traits like diabetes and psychiatric disorders are polygenic, influenced by many genetic variants. The omnigenic model suggests all expressed genes can impact disease-related genes. This study examines blood transcriptomic variations in psychiatric and neurological disorders to understand mRNA expression profiles and address field discrepancies. Animal models are explored for similar gene expressions. This study extensively searched GEO DataSets and ArrayExpress databases, identifying gene expression profiles associated with neuropsychiatric disorders. From GEO, 10,359 samples were found, with 30 series (1,897 samples) in the qualitative synthesis, revealing 1,364 differentially expressed genes in Schizophrenia, 134 in Bipolar Disorder, 11 in Autism Spectrum Disorder, and 2,784 in Alzheimer's Disorder. Comparisons with GWAS studies unveiled overlaps, with 81 genes for SCZ, two for BD, and 135 for ALZ. Notably, 441 genes were shared between ALZ and SCZ. Enrichment analyses indicated associations with signalling pathways. In animal models, 2,360 series were identified, with 175 in the qualitative synthesis, resulting in a meta-analysis focusing on ALZ with hippocampus tissue, revealing 14 consistently differentially expressed genes. Four overlapped with human data (ALOX5AP, P2RY13, RGS10, SH3GL1). These findings contribute to understanding shared and unique molecular signatures across neuropsychiatric disorders, bridging insights between human and animal models. The study efficiently identifies and tests consistent differentially expressed genes in psychiatric and neurological disorders, focusing on blood transcriptomes. Compared to transcriptome-wide or proteome-wide association studies, this approach analyses transcripts directly from individuals with disorders, offering real-world predictive capability. Shared genes between disorders suggest common molecular pathways, emphasizing the need for interdisciplinary approaches in understanding and treating psychiatric disorders. Limitations include sample characterization and the peripheral marker focus. Further investigations, including functional assays, are crucial for validation and extending these findings. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This study did not receive any funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: GEO datasets I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors