title: Genome-wide schizophrenia variant at MIR137 does not impact white matter microstructure in healthy participants.
abstract: A single nucleotide polymorphism (SNP rs1625579) within the micro-RNA 137 (MIR137) gene recently achieved strong genome-wide association with schizophrenia (SZ). However, the mechanisms by which SZ risk may be mediated by this variant are unknown. As miRNAs have the potential to influence oligodendrocyte development, we investigated whether this SNP was associated with variability in white matter (WM) microstructure. Diffusion tensor imaging (DTI) was conducted on 123 healthy participants genotyped for rs1625579. The analysis consisted of whole-brain tract-based spatial statistics and atlas-based tractography analysis of six major WM tracts known to be affected in SZ - the inferior longitudinal fasciculus, the uncinate fasciculus, the inferior fronto-occipital fasciculus, the anterior thalamic radiation, the cingulum bundle and the corpus callosum. No significant differences in either whole-brain fractional anisotropy or mean diffusivity between MIR137 genotype groups were observed (p>0.05). Similarly, atlas-based tractography of particular tracts implicated in SZ failed to reveal any significant differences between MIR137 genotype groups on measures of WM connectivity (p>0.05). In the absence of WM effects comparable to those reported for other SZ associated genes, these data suggest that MIR137 alone may not confer variability in these WM measures and therefore may not act in isolation for any effects that the variant may have on WM microstructure in SZ samples.
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Sinead
authors.initials: S
authors.lastname: Kelly
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Discipline of Biochemistry, School of Natural Sciences, National University of Ireland Galway, Ireland.
authors.forename: Derek W
authors.initials: DW
authors.lastname: Morris
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Omar
authors.initials: O
authors.lastname: Mothersill
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland; Transdisciplinary Science and Translational Prevention Program (TSTPP), Research Triangle Institute, Baltimore, MD, United States.
authors.forename: Emma Jane
authors.initials: EJ
authors.lastname: Rose
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Ciara
authors.initials: C
authors.lastname: Fahey
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Carol
authors.initials: C
authors.lastname: O'Brien
authors.affiliation: Department of Psychiatry, Royal College of Surgeons in Ireland, Ireland.
authors.forename: Erik
authors.initials: E
authors.lastname: O'Hanlon
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland.
authors.forename: Aiden P
authors.initials: AP
authors.lastname: Corvin
authors.affiliation: Neuropsychiatric Genetics Group, Department of Psychiatry, Trinity Centre for health Sciences, St. James's Hospital, Dublin 8, Ireland; Trinity College Institute for Neuroscience, Trinity College Dublin, Ireland; School of Psychology, National University of Ireland Galway, Ireland. Electronic address: gary.donohoe@NUIGalway.ie.
authors.forename: Gary
authors.initials: G
authors.lastname: Donohoe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D056324:Diffusion Tensor Imaging; D005260:Female; D056726:Genetic Association Studies; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology; D066127:White Matter / Q000033:anatomy & histology*; D055815:Young Adult
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs
keywords: DTI; GWAS; MIR137; Schizophrenia; White matter