Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder

Am J Hum Genet. 2004 Nov;75(5):862-72. doi: 10.1086/425586. Epub 2004 Sep 22.

Abstract

Schizophrenia, schizoaffective disorder, and bipolar disorder are common psychiatric disorders with high heritabilities and variable phenotypes. The Disrupted in Schizophrenia 1 (DISC1) gene, on chromosome 1q42, was originally discovered and linked to schizophrenia in a Scottish kindred carrying a balanced translocation that disrupts DISC1 and DISC2. More recently, DISC1 was linked to schizophrenia, broadly defined, in the general Finnish population, through the undertransmission to affected women of a common haplotype from the region of intron 1/exon 2. We present data from a case-control study of a North American white population, confirming the underrepresentation of a common haplotype of the intron 1/exon 2 region in individuals with schizoaffective disorder. Multiple haplotypes contained within four haplotype blocks extending between exon 1 and exon 9 are associated with schizophrenia, schizoaffective disorder, and bipolar disorder. We also find overrepresentation of the exon 9 missense allele Phe607 in schizoaffective disorder. These data support the idea that these apparently distinct disorders have at least a partially convergent etiology and that variation at the DISC1 locus predisposes individuals to a variety of psychiatric disorders.

MeSH terms

  • Adult
  • Bipolar Disorder / genetics*
  • Chromosomes, Human, Pair 1 / genetics*
  • European Continental Ancestry Group
  • Female
  • Genetic Markers / genetics
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Male
  • Nerve Tissue Proteins / genetics*
  • North America
  • Polymorphism, Single Nucleotide / genetics
  • Psychotic Disorders / genetics*
  • Schizophrenia / genetics*

Substances

  • DISC1 protein, human
  • Genetic Markers
  • Nerve Tissue Proteins