Failure to confirm genetic association between schizophrenia and markers on chromosome 1q23.3 in the region of the gene encoding the regulator of G-protein signaling 4 protein (RGS4).
The chromosome 1q23.3 region, which includes the RGS4 gene has been implicated in genetic susceptibility to schizophrenia by two linkage studies with lod scores of 6.35 and 3.20 and with positive lod between 2.00 and 3.00 scores in several other studies. Reduced post mortem RGS4 gene expression in the brain of schizophrenics was reported as well as positive allelic association between markers at the RGS4 gene locus and schizophrenia. We have attempted to replicate the finding of allelic association with schizophrenia in a UK based sample of 450 subjects with schizophrenia and 450 supernormal controls. We genotyped the same SNP marker alleles investigated in the earlier studies and also a di-nucleotide (GT)14 repeat microsatellite marker, which was 7 kb distal to RGS4. In the new UK sample there was no evidence for allelic or haplotypic association between RGS4 markers and schizophrenia. This might reflect genetic heterogeneity between the population samples, genotyping or other methodological problems. The finding weakens the evidence that mutations or variation in the RGS4 gene have an effect on schizophrenia susceptibility.
Rizig
Mie A
MA
Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, London, United Kingdom.
McQuillin
Andrew
A
Puri
Vinay
V
Choudhury
Khalid
K
Datta
Susmita
S
Thirumalai
Srinivasa
S
Lawrence
Jacob
J
Quested
Digby
D
Pimm
Jonathan
J
Bass
Nicholas
N
Lamb
Graham
G
Moorey
Helen
H
Badacsonyi
Allison
A
Kelly
Katie
K
Morgan
Jenny
J
Punukollu
Bhaskar
B
Kandasami
Gomathinayagam
G
Curtis
David
D
Gurling
Hugh
H
D000483:Alleles; D016022:Case-Control Studies; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D020710:RGS Proteins / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D006113:United Kingdom
D005819:Genetic Markers; D020710:RGS Proteins; C098799:RGS4 protein