Making the case for a candidate vulnerability gene in schizophrenia: Convergent evidence for regulator of G-protein signaling 4 (RGS4).
Both genetic and environmental factors have been associated with an increased risk for schizophrenia. These factors are not mutually exclusive; a single gene can be a genetic factor (due to a mutation in the gene sequence) and a target of a physiological response to an environmental stimulus, both with the common endpoint of altered expression of the gene. Regulator of G-protein signaling 4 (RGS4) has been implicated as such a gene from three lines of evidence. First, a subset of genetic studies revealed an association between schizophrenia and non-functional polymorphisms in the RGS4 gene. Second, across the cortical mantle the expression of RGS4 mRNA is decreased in a diagnosis-specific manner in subjects with schizophrenia. Third, neurobiological studies demonstrate that RGS4 is highly responsive to environmental stimuli and capable of modulating the function of G-protein coupled neurotransmitter receptors implicated in schizophrenia. RGS4 is an example of a molecule that may underlie increased vulnerability through either genetic or non-genetic mechanisms, which we suggest may be typical of other genes in a complex, polygenic disorder such as schizophrenia.
Levitt
Pat
P
Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee 37203, USA. pat.levitt@vanderbilt.edu
Ebert
Philip
P
Mirnics
Karoly
K
Nimgaonkar
Vishwajit L
VL
Lewis
David A
DA
D000818:Animals; D004777:Environment; D006801:Humans; D008954:Models, Biological; D009446:Neurobiology; D020710:RGS Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
D020710:RGS Proteins; C098799:RGS4 protein