title: Fine mapping by genetic association implicates the chromosome 1q23.3 gene UHMK1, encoding a serine/threonine protein kinase, as a novel schizophrenia susceptibility gene.
abstract: BACKGROUND
  Linkage studies by us and others have confirmed that chromosome 1q23.3 is a susceptibility locus for schizophrenia. Based on this information, several research groups have published evidence that markers within both the RGS4 and CAPON genes, which are 700 kb apart, independently showed allelic association with schizophrenia. Tests of allelic association with both of these genes in our case control sample were negative. Therefore, we carried out further fine mapping between the RGS4 and CAPON genes.
  
  
  METHODS
  Twenty-nine SNP and microsatellite markers in the 1q23.3 region were genotyped in the United Kingdom based sample of 450 cases and 450 supernormal control subjects.
  
  
  RESULTS
  We detected positive allelic association after the eighth marker was genotyped and found that three microsatellite markers (p = .011, p = .014, p = .049) and two SNPs (p = .004, p = .043) localized in the 700 kb region between the RGS4 and CAPON genes, within the UHMK1 gene, were associated with schizophrenia. Tests of significance for marker rs10494370 remained significant following Bonferroni correction (alpha = .006) for multiple tests. Tests of haplotypic association were also significant for UHMK1 (p = .009) using empirical permutation tests, which make it unnecessary to further correct for both multiple alleles and multiple markers.
  
  
  CONCLUSIONS
  These results provide preliminary evidence that the UHMK1 gene increases susceptibility to schizophrenia. Further confirmation in adequately powered samples is needed. UHMK1 is a serine threonine kinase nuclear protein and is highly expressed in regions of the brain implicated in schizophrenia.
authors.affiliation: Molecular Psychiatry Laboratory, Department of Mental Health Sciences, University College London Medical School, London, UK.
authors.forename: Vinay
authors.initials: V
authors.lastname: Puri
authors.forename: Andrew
authors.initials: A
authors.lastname: McQuillin
authors.forename: Khalid
authors.initials: K
authors.lastname: Choudhury
authors.forename: Susmita
authors.initials: S
authors.lastname: Datta
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pimm
authors.forename: Srinivasa
authors.initials: S
authors.lastname: Thirumalai
authors.forename: Robert
authors.initials: R
authors.lastname: Krasucki
authors.forename: Jacob
authors.initials: J
authors.lastname: Lawrence
authors.forename: Digby
authors.initials: D
authors.lastname: Quested
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bass
authors.forename: Helen
authors.initials: H
authors.lastname: Moorey
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: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping / Q000379:methods; D002878:Chromosomes, Human, Pair 1; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D018895:Microsatellite Repeats; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020710:RGS Proteins / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C488081:NOS1AP protein, human; D020710:RGS Proteins; C098799:RGS4 protein; D017346:Protein Serine-Threonine Kinases