title: Disrupted in schizophrenia 1 (DISC1): association with schizophrenia, schizoaffective disorder, and bipolar disorder.
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.
authors.affiliation: Section of Human Neurogenetics and Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Rockville, MD, USA. chodg@mail.nih.gov
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Judith
authors.initials: J
authors.lastname: Jaeger
authors.forename: Shalini
authors.initials: S
authors.lastname: Persaud
authors.forename: John M
authors.initials: JM
authors.lastname: Kane
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lipsky
authors.forename: Anil K
authors.initials: AK
authors.lastname: Malhotra
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009656:North America; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D044465:White People
chemical_list: C412476:DISC1 protein, human; D005819:Genetic Markers; D009419:Nerve Tissue Proteins