title: Polymorphisms in MIR137HG and microRNA-137-regulated genes influence gray matter structure in schizophrenia.
abstract: Evidence suggests that microRNA-137 (miR-137) is involved in the genetic basis of schizophrenia. Risk variants within the miR-137 host gene (MIR137HG) influence structural and functional brain-imaging measures, and miR-137 itself is predicted to regulate hundreds of genes. We evaluated the influence of a MIR137HG risk variant (rs1625579) in combination with variants in miR-137-regulated genes TCF4, PTGS2, MAPK1 and MAPK3 on gray matter concentration (GMC). These genes were selected based on our previous work assessing schizophrenia risk within possible miR-137-regulated gene sets using the same cohort of subjects. A genetic risk score (GRS) was determined based on genotypes of these four schizophrenia risk-associated genes in 221 Caucasian subjects (89 schizophrenia patients and 132 controls). The effects of the rs1625579 genotype with the GRS of miR-137-regulated genes in a three-way interaction with diagnosis on GMC patterns were assessed using a multivariate analysis. We found that schizophrenia subjects homozygous for the MIR137HG risk allele show significant decreases in occipital, parietal and temporal lobe GMC with increasing miR-137-regulated GRS, whereas those carrying the protective minor allele show significant increases in GMC with GRS. No correlations of GMC and GRS were found in control subjects. Variants within or upstream of genes regulated by miR-137 in combination with the MIR137HG risk variant may influence GMC in schizophrenia-related regions in patients. Given that the genes evaluated here are involved in protein kinase A signaling, dysregulation of this pathway through alterations in miR-137 biogenesis may underlie the gray matter loss seen in the disease.
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.|Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: C
authors.initials: C
authors.lastname: Wright
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.
authors.forename: C N
authors.initials: CN
authors.lastname: Gupta
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.
authors.forename: V
authors.initials: V
authors.lastname: Patel
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.|Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA.|Department of Electrical and Computer Engineering, University of New Mexico, Albuquerque, NM, USA.
authors.forename: V D
authors.initials: VD
authors.lastname: Calhoun
authors.affiliation: Translational Developmental Neuroscience Section, Department of Child and Adolescent Psychiatry, Faculty of Medicine, Technische Universität, Dresden, Germany.|Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.|Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, USA.
authors.forename: S
authors.initials: S
authors.lastname: Ehrlich
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Department of Radiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA.|Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: J R
authors.initials: JR
authors.lastname: Bustillo
authors.affiliation: Department of Neurosciences, University of New Mexico, Albuquerque, NM, USA.|Department of Psychiatry and Behavioral Sciences, University of New Mexico, Albuquerque, NM, USA.
authors.forename: N I
authors.initials: NI
authors.lastname: Perrone-Bizzozero
authors.affiliation: The Mind Research Network, Albuquerque, NM, USA.|Department of Psychology and Neuroscience Institute, Georgia State University, Atlanta, GA, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Turner
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D066128:Gray Matter / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000473:pathology*; D055815:Young Adult
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs
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