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.

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“…the relative anatomical or physiological strength of connections from either eye to individual cells in the primary visual cortex) and affects the maturation of dendritic spines (Mellios et al, 2011;Tognini et al, 2011). Thus, these studies showed for the first time a function of (Wright et al, 2016;Siegert et al, 2015;Lett et al, 2013) Idiopathic autism Multiple miRNAs (Wu et al, 2016;Mor et al, 2015;Mundalil Vasu et al, 2014) Fragile-X syndrome miR-9, miR-124 ) let-7b/c, miR-125a, miR-181a, miR-296, miR-342 (Wan et al, 2016 miR-125b, miR-132 (Edbauer et al, 2010) miR-125a (Muddashetty et al, 2011) miR-181d (Wang et al, 2015 Rett syndrome miR379-410 cluster and other miRNAs (Wu et al, 2010) let-7f (Mellios et al, 2014) miR132-212 cluster (Im et al, 2010) 377 miRNAs (e.g. miR-134, miR-383, miR-382, miR-182) (Cheng et al, 2014) miR-199a (Tsujimura et al, 2015) miRNAs in the activity-dependent maturation of neural circuits, a form of developmental synaptic plasticity, in the mammalian brain in vivo.…”

MicroRNAs in Schizophrenia: Implications for Synaptic Plasticity and Dopamine–Glutamate Interaction at the Postsynaptic Density. New Avenues for Antipsychotic Treatment Under a Theranostic Perspective

“…[75] strongly predicting an earlier age-at-onset of psychosis, reduced white matter integrity, and cognitive deficits in combination with higher severity of negative symptoms [84][85][86]. Moreover, two SNPs in the Dgcr8 and Dicer gene have been significantly associated with an altered schizophrenia risk in a Chinese schizophrenia patient cohort, suggesting that the specific genetic variants in miRNA machinery genes may affect the susceptibility to the disease [87].…”

Unmet needs in paediatric psychopharmacology: Present scenario and future perspectives

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