Genetic Analysis of RASD1 as a Candidate Gene for Schizophrenia

Abstract

RASD1 encodes Dexamethasone-induced Ras-related protein 1 (Dexras1), a protein with a critical role in signal transduction in neurons. There is a strong suspicion that dysfunction of Dexras1 might contribute to the pathogenesis of neuropsychiatric diseases. Related to its functions in intracellular signaling pathways, Dexras1 has a potential role in the etiology of schizophrenia because of its close interaction with NOS1, NOS1AP, and NMDAR, which have previously been associated with schizophrenia. To investigate the association of RASD1 variants with schizophrenia in a selected cohort from Turkey. A case-control study. We performed targeted sequencing for the two exons, single intron, and untranslated regions of RASD1 gene in 200 individuals with schizophrenia and 100 healthy controls of Turkish origin. Two rare variants, RASD1 (NM_016084.5): c.722A>T and c*31G>A were identified in individuals with schizophrenia but not in any controls. The c.722A>T was found in a single individual with schizophrenia and is a missense heterozygous variant in the second exon of RASD1, which is extremely rare in GnomAD. The other variant, c*31G>A, which was found in another individual from this schizophrenia cohort, has not been reported previously. Seven previously identified common single nucleotide polymorphisms were also detected; however, they were not significantly associated with schizophrenia in this study cohort. Our findings suggest that rare variants of RASD1 might be contributing to the etiopathogenesis of schizophrenia. Further studies are needed to elucidate the underlying mechanism of this association.