title: Association of DISC1 and TSNAX genes and affective disorders in the depression case-control (DeCC) and bipolar affective case-control (BACCS) studies.
abstract: The gene known as Disrupted-in-Schizophrenia-1, DISC1, was originally discovered in a large family, in which it also co-segregated with bipolar affective disorder (BD) and with major depressive disorder (MDD). The TSNAX (Translin-associated factor X) gene, located immediately upstream of DISC1, has also been suggested as a candidate gene in relation to psychiatric illness, as one transcript resulting from intergenic splicing encodes a novel TSNAX-DISC1 fusion protein. We explored the TSNAX-DISC1 gene region for an association with BD and MDD in a sample of 1984 patients (1469 MDD, 515 BD) and 1376 ethnically matched controls. Eight single nucleotide polymorphisms (SNPs) within the TSNAX-DISC1 region (rs766288, rs3738401, rs2492367, rs6675281, rs12133766, rs1000731, rs7546310 and rs821597) were investigated using the SNPlex Genotyping System. We found a significant allelic and genotypic association of the TSNAX-DISC1 gene region with BD, whereas a haplotypic association was found for both BD and MDD. Therefore, our results suggest an association between the TSNAX-DISC1 region and both forms of affective disorders, and support the hypothesis that a portion of the genotypic overlap between schizophrenia and affective disorders is attributable to this gene.
authors.affiliation: MRC SGDP Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK. alexandra.schosser@iop.kcl.ac.uk
authors.forename: A
authors.initials: A
authors.lastname: Schosser
authors.forename: D
authors.initials: D
authors.lastname: Gaysina
authors.forename: S
authors.initials: S
authors.lastname: Cohen-Woods
authors.forename: P C
authors.initials: PC
authors.lastname: Chow
authors.forename: L
authors.initials: L
authors.lastname: Martucci
authors.forename: N
authors.initials: N
authors.lastname: Craddock
authors.forename: A
authors.initials: A
authors.lastname: Farmer
authors.forename: A
authors.initials: A
authors.lastname: Korszun
authors.forename: C
authors.initials: C
authors.lastname: Gunasinghe
authors.forename: J
authors.initials: J
authors.lastname: Gray
authors.forename: L
authors.initials: L
authors.lastname: Jones
authors.forename: F
authors.initials: F
authors.lastname: Tozzi
authors.forename: J
authors.initials: J
authors.lastname: Perry
authors.forename: P
authors.initials: P
authors.lastname: Muglia
authors.forename: M J
authors.initials: MJ
authors.lastname: Owen
authors.forename: I W
authors.initials: IW
authors.lastname: Craig
authors.forename: P
authors.initials: P
authors.lastname: McGuffin
mesh_terms: D000328:Adult; D001714:Bipolar Disorder / Q000235:genetics*; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000235:genetics*; D003863:Depression / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C412476:DISC1 protein, human; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C498305:TSNAX protein, human