The genome-wide supported microRNA-137 variant predicts phenotypic heterogeneity within schizophrenia

T. A. Lett, M. M. Chakavarty, D. Felsky, E. J. Brandl, A. K. Tiwari, V. F. Gonçalves, T. K. Rajji, Z. J. Daskalakis, H. Y. Meltzer, J. A. Lieberman, J. P. Lerch, B. H. Mulsant, J. L. Kennedy, A. N. Voineskos*

*Corresponding author for this work

Research output: Contribution to journalArticle

84 Scopus citations

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; F 1,506 =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 (F 3,209 =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 languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalMolecular Psychiatry
Volume18
Issue number4
DOIs
StatePublished - Apr 2013

Keywords

  • MIR137
  • age-At-onset
  • genetics
  • heterogeneity
  • imaging
  • schizophrenia

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience

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