Current progress in understanding schizophrenia using genomics and pluripotent stem cells: A meta-analytical overview

Abstract

Schizophrenia (SCZ) is a complex, heritable and polygenic neuropsychiatric disease, which disables the patients as well as decreases their life expectancy and quality of life. Common and rare variants studies on SCZ subjects have provided >100 genomic loci that hold importance in the context of SCZ pathophysiology. Transcriptomic studies from clinical samples have informed about the differentially expressed genes (DEGs) and non-coding RNAs in SCZ patients. Despite these advancements, no causative genes for SCZ were found and hence SCZ is difficult to recapitulate in animal models. In the last decade, induced Pluripotent Stem Cells (iPSCs)-based models have helped in understanding the neural phenotypes of SCZ by studying patient iPSC-derived 2D neuronal cultures and 3D brain organoids. Here, we have aimed to provide a simplistic overview of the current progress and advancements after synthesizing the enormous literature on SCZ genetics and SCZ iPSC-based models. Although further understanding of SCZ genetics and pathophysiological mechanisms using these technological advancements is required, the recent approaches have allowed to delineate important cellular mechanisms and biological pathways affected in SCZ.

Keywords: GWAS; Non-coding RNAs; Patient-iPSC-derived neurons; RDoC; Schizophrenia; Transcriptomics; iPSC.