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 familybased
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.
