  The Disrupted in Schizophrenia Gene 1 (DISC1) plays a role in both neural
signalling and development and is associated with schizophrenia, although its
links to altered brain structure and function in this disorder are not fully
established. Here we have used structural and functional MRI to investigate
links with six DISC1 single nucleotide polymorphisms (SNPs). We employed a
brain-wide association analysis (BWAS) together with a Jacknife internal
validation approach in 46 schizophrenia patients and 24 matched healthy control
subjects. Results from structural MRI showed significant associations between
all six DISC1 variants and gray matter volume in the precuneus, post-central
gyrus and middle cingulate gyrus. Associations with specific SNPs were found
for rs2738880 in the left precuneus and right post-central gyrus, and rs1535530
in the right precuneus and middle cingulate gyrus. Using regions showing
structural associations as seeds a resting-state functional connectivity
analysis revealed significant associations between all 6 SNPS and connectivity
between the right precuneus and inferior frontal gyrus. The connection between
the right precuneus and inferior frontal gyrus was also specifically associated
with rs821617. Importantly schizophrenia patients showed positive correlations
between the six DISC-1 SNPs associated gray matter volume in the left precuneus
and right post-central gyrus and negative symptom severity. No correlations
with illness duration were found. Our results provide the first evidence
suggesting a key role for structural and functional connectivity associations
between DISC1 polymorphisms and the precuneus in schizophrenia.
