Impact of a microRNA MIR137 susceptibility variant on brain function in people at high genetic risk of schizophrenia or bipolar disorder

Abstract

A recent mega-analysis combining genome-wide association study data from over 40 000 individuals identified novel genetic loci associated with schizophrenia (SCZ) at genome-wide significance level. The strongest finding was a locus within an intron of a putative primary transcript for microRNA MIR137. In the current study, we examine the impact of variation at this locus (rs1625579, G/T; where T is the common and presumed risk allele) on brain activation during a sentence completion task that differentiates individuals with SCZ, bipolar disorder (BD), and their relatives from controls. We examined three groups of individuals performing a sentence completion paradigm: (i) individuals at high genetic risk of SCZ (n44), (ii) individuals at high genetic risk of BD (n90), and (iii) healthy controls (n81) in order to test the hypothesis that genotype at rs1625579 would influence brain activation. Genotype groups were assigned as RISK for GT and GG individuals, and RISK for TT homozygotes. The main effect of genotype was significantly greater activation in the RISK individuals in the posterior right medial frontal gyrus, BA 6. There was also a significant genotype group interaction in the left amygdala and left pre/postcentral gyrus. This was due to differences between the controls (where individuals with the RISK genotype showed greater activation than RISK subjects) and the SCZ high-risk group, where the opposite genotype effect was seen. These results suggest that the newly identified SCZ locus may influence brain activation in a manner that is partly dependent on the presence of existing genetic susceptibility for SCZ. © 2012 American College of Neuropsychopharmacology.