title: A schizophrenia risk gene, ZNF804A, is associated with brain white matter microstructure.
abstract: Genome-wide association studies have provided strong evidence for association of the SNP rs1344706 in the ZNF804A gene with schizophrenia and bipolar disorder. Neuroimaging studies have suggested that variation at rs1344706 may be associated with neural endophenotypes such as white matter volumes and densities. However, analyses of white matter microstructure using diffusion tensor imaging (DTI) have produced conflicting results. We examined the association between rs1344706 and white matter microstructure in 107 healthy individuals using tract-based spatial statistics (TBSS). TBSS analysis showed significant association between the risk allele and lower fractional anisotropy in the corpus callosum, left forceps minor, and right parietal white matter (p<.05; FWE corrected). Post-hoc analyses indicated that this association was largely driven by alterations in radial diffusivity, consistent with an effect of genotype on myelination. In light of the strong DTI evidence for white matter microstructural abnormalities in schizophrenia, the current results implicate a potential mechanism for schizophrenia risk formation by ZNF804A rs1344706 genotype.
authors.affiliation: Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, MS, USA. Electronic address: tikuta@olemiss.edu.
authors.forename: T
authors.initials: T
authors.lastname: Ikuta
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
authors.forename: B D
authors.initials: BD
authors.lastname: Peters
authors.affiliation: Division of Medical Genetics, Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, NY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Guha
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA.
authors.forename: M
authors.initials: M
authors.lastname: John
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Hofstra North Shore-LIJ School of Medicine, Departments of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
authors.forename: K H
authors.initials: KH
authors.lastname: Karlsgodt
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Hofstra North Shore-LIJ School of Medicine, Departments of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
authors.forename: T
authors.initials: T
authors.lastname: Lencz
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Hofstra North Shore-LIJ School of Medicine, Departments of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
authors.forename: P R
authors.initials: PR
authors.lastname: Szeszko
authors.affiliation: Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA; Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, NY, USA; Hofstra North Shore-LIJ School of Medicine, Departments of Psychiatry and Molecular Medicine, Hempstead, NY, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Malhotra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016880:Anisotropy; D001921:Brain / Q000033:anatomy & histology*; D002648:Child; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D007839:Functional Laterality / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D066127:White Matter / Q000033:anatomy & histology*; D055815:Young Adult
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human
keywords: Diffusion tensor imaging; Endophenotype; Genetics; Schizophrenia; White matter; ZNF804A