title: C18orf1 located on chromosome 18p11.2 may confer susceptibility to schizophrenia.
abstract: The pericentromeric region of chromosome 18, especially 18p11.2, is described as a schizophrenia susceptibility locus. We had previously cloned two novel brain-derived transcripts from this region: the gene for a second human myo-inositol monophosphatase (IMPA2) and a gene of unknown function, C18orf1. Recently, we reported a distortion of transmission of the tandem repeat marker D18S852, embedded in the 3'-untranslated region of C18orf1, in schizophrenia, using a family-based association test. A subsequent case-control study also revealed a significant association between the haplotype constructed from D18S852 and the 6409T>C polymorphism located in C18orf1 and schizophrenia. In the present study, we screened the C18orf1 gene for mutations and identified a novel single nucleotide polymorphism (SNP), -96T>C in exon 2. This SNP showed significant genotypic (P = 0.048) and allelic association (P = 0.005) with schizophrenia in a case-control study. The distributions of haplotypes defined by D18S852 and -96T>C were different between control and schizophrenia groups (P = 0.021). These findings suggest that C18orf1 or a gene nearby may contribute to the overall genetic risk for schizophrenia.
authors.affiliation: Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako-city, Saitama, Japan.
authors.forename: Mika
authors.initials: M
authors.lastname: Kikuchi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamada
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toyota
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D002503:Centromere / Q000235:genetics; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D003596:Cytosine; D005091:Exons / Q000235:genetics; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000235:genetics*; D020080:Tandem Repeat Sequences / Q000235:genetics; D013941:Thymine
chemical_list: C111334:LDLRAD4 protein, human; D008565:Membrane Proteins; D003596:Cytosine; D010744:Phosphoric Monoester Hydrolases; C021822:myo-inositol-1 (or 4)-monophosphatase; D013941:Thymine