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Published on: June 15, 2011
Genetic Analysis of RASD1 as a Candidate Gene for Schizophrenia
Ceren Damla Durmaz1,2, Halil Gürhan Karabulut1, Meram Can Saka3
1Department of Medical Genetics, School of Medicine, Ankara University, Ankara, Turkey
Background:
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.
Aims:
To investigate the association of RASD1 variants with schizophrenia in a selected cohort from Turkey.
Study Design:
A case-control study.
Methods:
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.
Results:
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.
Conclusion:
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.
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