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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.

Original publication

DOI

10.1038/mp.2013.17

Type

Journal article

Journal

Mol Psychiatry

Publication Date

04/2013

Volume

18

Pages

443 - 450

Keywords

Adult, Age of Onset, Atrophy, Case-Control Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Hippocampus, Humans, Hypertrophy, Lateral Ventricles, Male, MicroRNAs, Nerve Fibers, Myelinated, Phenotype, Polymorphism, Single Nucleotide, Psychotic Disorders, Schizophrenia, Schizophrenic Psychology