title: 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=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.
authors: Division of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, UK. heather.whalley@ed.ac.uk
authors: Heather C
authors: HC
authors: Whalley
authors: Martina
authors: M
authors: Papmeyer
authors: Liana
authors: L
authors: Romaniuk
authors: Emma
authors: E
authors: Sprooten
authors: Eve C
authors: EC
authors: Johnstone
authors: Jeremy
authors: J
authors: Hall
authors: Stephen M
authors: SM
authors: Lawrie
authors: Kathryn L
authors: KL
authors: Evans
authors: Hilary P
authors: HP
authors: Blumberg
authors: Jessika E
authors: JE
authors: Sussmann
authors: Andrew M
authors: AM
authors: McIntosh
mesh_terms: D001714:Bipolar Disorder / Q000235:genetics* / Q000523:psychology*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping; D004247:DNA / Q000235:genetics; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009483:Neuropsychological Tests; D016133:Polymerase Chain Reaction; D011569:Psychiatric Status Rating Scales; D011930:Reaction Time / Q000502:physiology; D012306:Risk; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012565:Schizophrenic Psychology; D013702:Temporal Lobe / Q000473:pathology; D055815:Young Adult
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs; D004247:DNA