Whalley, Heather C, Papmeyer, Martina, Romaniuk, Liana, Sprooten, Emma, Johnstone, Eve C, Hall, Jeremy ORCID: https://orcid.org/0000-0003-2737-9009, Lawrie, Stephen M, Evans, Kathryn L, Blumberg, Hilary P, Sussmann, Jessika E and McIntosh, Andrew M 2012. Impact of a microRNA MIR137 susceptibility variant on brain function in people at high genetic risk of schizophrenia or bipolar disorder. Neuropsychopharmacology 37 (12) , pp. 2720-2729. 10.1038/npp.2012.137 |
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=44), (ii) individuals at high genetic risk of BD (n=90), and (iii) healthy controls (n=81) 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.
Item Type: | Article |
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Date Type: | Publication |
Status: | Published |
Schools: | MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Medicine Neuroscience and Mental Health Research Institute (NMHRI) |
Subjects: | R Medicine > R Medicine (General) |
Publisher: | Nature Publishing Group |
ISSN: | 0893-133X |
Last Modified: | 31 Oct 2022 08:59 |
URI: | https://orca.cardiff.ac.uk/id/eprint/79429 |
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