Integrated bioinformatics and statistical approach to identify the common molecular mechanisms of obesity that are linked to the development of two psychiatric disorders: Schizophrenia and major depressive disorder

Abstract

Obesity is a chronic multifactorial disease characterized by the accumulation of body fat and serves as a gateway to a number of metabolic-related diseases. Epidemiologic data indicate that Obesity is acting as a risk factor for neuro-psychiatric disorders such as schizophrenia, major depression disorder and vice versa. However, how obesity may biologically interact with neurodevelopmental or neurological psychiatric conditions influenced by hereditary, environmental, and other factors is entirely unknown. To address this issue, we have developed a pipeline that integrates bioinformatics and statistical approaches such as transcriptomic analysis to identify differentially expressed genes (DEGs) and molecular mechanisms in patients with psychiatric disorders that are also common in obese patients. Biomarker genes expressed in schizophrenia, major depression, and obesity have been used to demonstrate such relationships depending on the previous research studies. The highly expressed genes identify commonly altered signalling pathways, gene ontology pathways, and gene-disease associations across disorders. The proposed method identified 163 significant genes and 134 significant pathways shared between obesity and schizophrenia. Similarly, there are 247 significant genes and 65 significant pathways that are shared by obesity and major depressive disorder. These genes and pathways increase the likelihood that psychiatric disorders and obesity are pathogenic. Thus, this study may help in the development of a restorative approach that will ameliorate the bidirectional relation between obesity and psychiatric disorder. Finally, we also validated our findings using genome-wide association study (GWAS) and whole-genome sequence (WGS) data from SCZ, MDD, and OBE. We confirmed the likely involvement of four significant genes both in transcriptomic and GWAS/WGS data. Moreover, we have performed co-expression cluster analysis of the transcriptomic data and compared it with the results of transcriptomic differential expression analysis and GWAS/WGS.