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A single nucleotide polymorphism (rs7914558) within the cyclin M2
(CNNM2) gene was recently identified as a common risk
variant for schizophrenia. The mechanism by which CNNM2
confers risk is unknown.
To determine the impact of the rs7914558 risk ‘A’ allele
on measures of neurocognition, social cognition and brain structure.
Patients with schizophrenia (n = 400) and healthy
controls (n = 160) completed measures of
neuropsychological function and social cognition. Structural magnetic
resonance imaging data were also acquired from an overlapping sample of
Irish healthy controls (n = 159) and an independent
sample of Italian patients (n = 82) and healthy controls
(n = 39).
No effects of genotype on neuropsychological test performance were
observed. However, a dosage effect of the risk allele was found for an
index of social cognition (i.e. attributional style), such that risk
status was associated with reduced self-serving bias across groups
(GG>AG>AA, P<0.05). Using voxel-based
morphometry to investigate neuroanatomical regions putatively supporting
social cognition, risk carriers had relatively increased grey matter
volume in the right temporal pole and right anterior cingulate cortex
(Pcorrected<0.05) in the Irish healthy controls sample;
neuroanatomical associations between CNNM2 and grey
matter volume in anterior cingulate cortex were also observed in the
Italian schizophrenia and healthy controls samples.
Although the biological role of CNNM2 in schizophrenia
remains unknown, these data suggest that this CNNM2 risk
variant rs7914558 may have an impact on neural systems relevant to social
cognition. How such effects may mediate the relationship between genotype
and disease risk remains to be established.
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