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DISC1 gene variants show mixed associations with psychiatric illness]]>

Posted by admin on April 06th, 2010

06
Apr

Disrupted in schizophrenia 1 (DISC1) gene variants play a role in the development of psychiatric illness yet there is significant heterogeneity in clinically relevant variants between populations, say international scientists.

Although schizophrenia, schizoaffective disorder, bipolar disorder (BD), major depression, autism, and Asperger syndrome have all been linked to DISC1, no actual causal variants have been identified.

William Hennah, from the University of Edinburgh, and colleagues therefore studied 1275 individuals with schizophrenia, nearly 2000 with BD, and more than 2000 healthy controls from four European centers. All participants were genotyped for the presence of 75 single nucleotide polymorphisms (SNPs) in the translin-associated protein X and DISC1 genes, of which 67 were suitable for analysis.

For the combined sample, no SNP survived permutation correction or was significantly associated with schizophrenia or BD. However, the rs1538979 SNP was significantly associated with BD I males in the Finnish group and the rs821577 SNP was significantly linked with BD females in the London group, at odds ratios of 2.73 and 1.64, respectively.

Although unable to survive corrected analysis, the rs821577 SNP G allele was associated with BD in the combined group and BD females, at odds ratios of 1.28 and 1.44, respectively.

Additionally, the rs1538979 SNP T allele was a risk factor for BD in females in the London group and was protective against in schizophrenia in men in the Aberdeen group at odds ratios of 1.50 and 0.55, respectively.

Further analysis revealed that the rs821633 SNP together with the T allele of the rs1538979 SNP were associated with an increased risk for schizophrenia in females. Interestingly, the rs1538979 SNP was a risk factor only in the presence of the rs821633 SNP, while the rs821633 SNP was protective on its own.

The team concludes in the journal Molecular Psychiatry: “Our data provide further genetic support for a role of DISC1 in psychiatric illness, with the same variants on the same gene modulating risk to both BD and schizophrenia, further substantiating the hypothesis that these two separate disorders have overlapping genetic risks.”

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