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 (n ¼ 44), (ii) individuals at high genetic risk of BD (n ¼ 90), and (iii) healthy controls (n ¼ 81) in order to test the hypothesis that genotype at rs1625579 would influence brain activation. Genotype groups were assigned as 'RISKÀ' for GT and GG individuals, and 'RISK + ' for TT homozygotes. The main effect of genotype was significantly greater activation in the RISKÀ 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 RISKÀ 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.

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

“…The analysis of the relationship between rs1625579 genotypes and miR-137 expression in the postmortem DLPFC revealed a significantly lower miR-137 expression level in the homozygous TT subjects compared to TG and GG subjects in the control group [82]. Moreover, homozygous TT individuals at high genetic risk for schizophrenia exhibited a lower activation in the posterior right medial frontal gyrus compared to healthy controls after a sentence completion task that differentiates individuals with schizophrenia and their relatives from controls [83]. Further studies demonstrated that the risk variant rs1625579 might substantially influence phenotypic variability in schizophrenia, with the miR-137 risk genotype Table 1 The miRNA abnormalities in schizophrenia and bipolar disorder patient brain tissues…”

MicroRNA and Posttranscriptional Dysregulation in Psychiatry

“…and qRT-PCR validation and discovered just one miRNA, miR29c, to be upregulated. The SNP rs1625579, which affects miR-137 in SZ, was also found to be functionally associated with individuals at risk of BD (45).…”

The consequences of suggesting false childhood food events

“…Mega-analysis has advantages over meta-analysis in that datasets can be combined to enhance statistical power, permitting examination of hypotheses that cannot be tested within single studies. This approach has been used to combine datasets in areas such as genetics (Whalley et al, 2012), functional neuroimaging (Hallahan et al, 2011), and psychiatric treatment (de Maat et al, 2008;Thase et al, 1997). The current study used the combined dataset to address three novel goals: (1) to test the direct versus indirect (mediated by autobiographical belief) effects of suggestion on suggestion-related preferences and behavior intention; (2) to examine the impact of the development (x), which in turn influence behavior (y).…”