title: The genome-wide supported microRNA-137 variant predicts phenotypic heterogeneity within schizophrenia.
abstract: We examined the influence of the genome-wide significant schizophrenia risk variant rs1625579 near the microRNA (miRNA)-137 (MIR137) gene on well-established sources of phenotypic variability in schizophrenia: age-at-onset of psychosis and brain structure. We found that the MIR137 risk genotype strongly predicts an earlier age-at-onset of psychosis across four independently collected samples of patients with schizophrenia (n=510; F1,506=17.7, P=3.1 × 10(-5)). In an imaging-genetics subsample that included additional matched controls (n=213), patients with schizophrenia who had the MIR137 risk genotype had reduced white matter integrity (F3,209=13.6, P=3.88 × 10(-8)) throughout the brain as well as smaller hippocampi and larger lateral ventricles; the brain structure of patients who were carriers of the protective allele was no different from healthy control subjects on these neuroimaging measures. Our findings suggest that MIR137 substantially influences variation in phenotypes that are thought to have an important role in clinical outcome and treatment response. Finally, the possible consequences of genetic risk factors may be distinct in patients with schizophrenia compared with healthy controls.
authors: Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors: T A
authors: TA
authors: Lett
authors: M M
authors: MM
authors: Chakravarty
authors: M M
authors: MM
authors: Chakavarty
authors: D
authors: D
authors: Felsky
authors: E J
authors: EJ
authors: Brandl
authors: A K
authors: AK
authors: Tiwari
authors: V F
authors: VF
authors: Gonçalves
authors: T K
authors: TK
authors: Rajji
authors: Z J
authors: ZJ
authors: Daskalakis
authors: H Y
authors: HY
authors: Meltzer
authors: J A
authors: JA
authors: Lieberman
authors: J P
authors: JP
authors: Lerch
authors: B H
authors: BH
authors: Mulsant
authors: J L
authors: JL
authors: Kennedy
authors: A N
authors: AN
authors: Voineskos
mesh_terms: D000328:Adult; D017668:Age of Onset; D001284:Atrophy; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D006984:Hypertrophy; D020547:Lateral Ventricles / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011618:Psychotic Disorders / Q000235:genetics; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D012565:Schizophrenic Psychology
chemical_list: D035683:MicroRNAs