Association of DISC1 and TSNAX genes and affective disorders in the depression case-control (DeCC) and bipolar affective case-control (BACCS) studies.
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.
Schosser
A
A
MRC SGDP Centre, Institute of Psychiatry, King's College London, De Crespigny Park, London, UK. alexandra.schosser@iop.kcl.ac.uk
Gaysina
D
D
Cohen-Woods
S
S
Chow
P C
PC
Martucci
L
L
Craddock
N
N
Farmer
A
A
Korszun
A
A
Gunasinghe
C
C
Gray
J
J
Jones
L
L
Tozzi
F
F
Perry
J
J
Muglia
P
P
Owen
M J
MJ
Craig
I W
IW
McGuffin
P
P
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*
C412476:DISC1 protein, human; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C498305:TSNAX protein, human