Effect of DISC1 SNPs on brain structure in healthy controls and patients with a history of psychosis

Abstract

Disrupted-in-Schizophrenia-1 (DISC1) has been suggested as a susceptibility locus for a broad spectrum of psychiatric disorders. Risk variants have been associated with brain structural changes, which overlap alterations reported in schizophrenia and bipolar disorder patients. We used genome-wide genotyping data for a Norwegian sample of healthy controls (n = 171) and patients with a history of psychosis (n = 184), to investigate 61 SNPs in the DISC1 region for putative association with structural magnetic resonance imaging (sMRI) measures (hippocampal volume; mean cortical thickness; and total surface area, as well as cortical thickness and area divided into four lobar measures). SNP rs821589 was associated with mean temporal and total brain cortical thickness in controls (P(adjusted) = 0.009 and 0.02, respectively), but not in patients. SNPs rs11122319 and rs1417584 were associated with mean temporal cortical thickness in patients (P(adjusted) = 0.04 and 0.03, respectively), but not in controls, and both SNPs have previously been highly associated with DISC1 gene expression. There were significant genotype × case-control interactions. There was no significant association between SNPs and cortical area or hippocampal volume in controls, or with any of the structural measures in cases, after correction for multiple comparisons. In conclusion, DISC1 SNPs might impact brain structural variation, possibly differently in psychosis patients versus controls, but independent replication will be needed to confirm our findings.