title: 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).
abstract: 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.
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, Windeyer Institute of Medical Sciences, London, United Kingdom.
authors.forename: Mie A
authors.initials: MA
authors.lastname: Rizig
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Vinay
authors.initials: V
authors.lastname: Puri
authors.forename: Khalid
authors.initials: K
authors.lastname: Choudhury
authors.forename: Susmita
authors.initials: S
authors.lastname: Datta
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Thirumalai
authors.forename: Jacob
authors.initials: J
authors.lastname: Lawrence
authors.forename: Digby
authors.initials: D
authors.lastname: Quested
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pimm
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bass
authors.forename: Graham
authors.initials: G
authors.lastname: Lamb
authors.forename: Helen
authors.initials: H
authors.lastname: Moorey
authors.forename: Allison
authors.initials: A
authors.lastname: Badacsonyi
authors.forename: Katie
authors.initials: K
authors.lastname: Kelly
authors.forename: Jenny
authors.initials: J
authors.lastname: Morgan
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Punukollu
authors.forename: Gomathinayagam
authors.initials: G
authors.lastname: Kandasami
authors.forename: David
authors.initials: D
authors.lastname: Curtis
authors.forename: Hugh
authors.initials: H
authors.lastname: Gurling
mesh_terms: 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
chemical_list: D005819:Genetic Markers; D020710:RGS Proteins; C098799:RGS4 protein