Association study of polymorphisms in the 5' upstream region of human DISC1 gene with schizophrenia

Neurosci Lett. 2004 Sep 16;368(1):41-5. doi: 10.1016/j.neulet.2004.06.048.


Disrupted-in-Schizophrenia-1 (DISC1) is a gene in which a mutant truncation by a balanced t(1;11)(p42.1;q14.3) translocation is segregated with major psychiatric illness with a predominance of schizophrenic symptomatology in a large Scottish family. However, no functional polymorphisms have been detected that are associated with schizophrenia in general populations. As prior polymorphism searches in DISC1 have been focused on coding exons and flanking introns, the present study examined sequence variations in the 5' upstream region of DISC1. Screening of exon 1 through to approximately 1.0 kb upstream of exon 1 identified 6 polymorphisms, including 2 novel variants, -94C>A and -199(CG)(n). We tested these variants for associations with schizophrenia in the first set of a case (n = 198) and control (n = 198) panel, and found significant results with -274G>C (genotypic P = 0.01) and -215(TG)(n) (genotypic P = 0.039). However, we failed to replicate these associations in a second, larger independent patient (n = 532) and control (n = 519) sample. These results suggest that the genomic interval of DISC1 probably involved in transcriptional regulation does not display major genetic relevance in Japanese schizophrenia patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Flanking Region / genetics*
  • Alleles
  • Amino Acid Sequence
  • DNA / genetics
  • DNA Primers
  • Female
  • Gene Expression Regulation / genetics*
  • Genotype
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Nerve Tissue Proteins / genetics*
  • Polymorphism, Genetic / genetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Schizophrenia / genetics*
  • Transcriptional Activation / genetics


  • DISC1 protein, human
  • DNA Primers
  • Nerve Tissue Proteins
  • DNA