Association of RGS2 and RGS5 variants with schizophrenia symptom severity.
BACKGROUND
Several lines of evidence indicate that Regulator of G Protein Signaling 4 (RGS4) contributes to schizophrenia vulnerability. RGS4 is one of a family of molecules that modulate signaling via G-protein coupled receptors. Five genes encoding members of this family (RGS2, RGS4, RGS5, RGS8 and RGS16) map to chromosome 1q23.3-1q31. Due to overlapping cellular functions and chromosomal proximity, we hypothesized that multiple RGS genes may contribute to schizophrenia severity and treatment responsiveness.


METHODS
Subjects were 750 individuals with schizophrenia who participated in the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE). Inferred ancestries were: 221 (30%) 'Africa only', 422 (56%) 'Europe only' and 107 (14%) 'Other'. Fifty-nine single nucleotide polymorphisms (SNPs) in or near the RGS5, RGS16, RGS8 and RGS2 genes were genotyped. Multiple linear regression was used to analyze association of markers with Positive and Negative Symptoms Scale (PANSS) total scores at baseline and throughout antipsychotic treatment.


RESULTS
RGS5 marker rs10799902 was associated with altered baseline PANSS total score in both the Africa only (P=0.0440) and Europe only (P=0.0143) strata, although neither association survived multiple comparisons correction. A common five-marker haplotype of the RGS2 gene was associated with more severe baseline PANSS total score in the Europe only strata (global P=0.0254; haplotype-specific P=0.0196). In contrast to RGS4, none of the markers showed association with antipsychotic treatment response.


CONCLUSIONS
RGS2 and RGS5 genotypes predicted severity of baseline symptoms in schizophrenia. Although these analyses are exploratory and replication is required, these data suggest a possible role for multiple RGS proteins in schizophrenia.
Campbell
Daniel B
DB
Department of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA. daniel.campbell@vanderbilt.edu
Lange
Leslie A
LA
Skelly
Tara
T
Lieberman
Jeffrey
J
Levitt
Pat
P
Sullivan
Patrick F
PF
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D044383:Black People; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D020710:RGS Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D044465:White People
D020710:RGS Proteins; C087182:RGS2 protein, human; C491349:RGS5 protein, human