title: Effects of ankyrin 3 gene risk variants on brain structures in patients with bipolar disorder and healthy subjects.
abstract: OBJECTIVE
  The intronic single-nucleotide polymorphism rs10994336 of the ankyrin 3 gene (ANK3 ) is one of the genome-wide supported risk variants for bipolar disorder (BD), and the T-allele of rs10761482 is also reported to have relevance to BD. We investigated the effect of ANK3 rs10761482 genetic variation on brain structure.
  
  
  METHODS
  Subjects were 43 BD patients and 229 healthy volunteers. We evaluated the effects of ANK3 rs10761482 genetic variation on diagnosis, and of the genotype-by-diagnosis interaction on the brain structure and the degree of age-related brain atrophy on magnetic resonance imaging data evaluated by voxel-based morphometry.
  
  
  RESULTS
  BD patients showed significantly lower fractional anisotropy value in the bilateral parietal regions, left fronto-occipital fasciculus, and corpus callosum, compared to healthy subjects. Further, we found considerable decreases of fractional anisotropy in the forceps minor in non-T-allele BD patients compared with the T-carrier patient group. We also found significant lessening of age-related brain atrophy in the T-allele carrier groups compared with the non-T-allele carrier groups in the area around the cerebrospinal space, cingulate cortices, and cerebellum.
  
  
  CONCLUSIONS
  Our results suggest the influence of the ANK3 on age-related brain atrophy. The ankyrin 3 genotype may be associated with pathogenesis of age-related neurodegeneration, and, in part, of BD.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hori
authors.affiliation: Department of Radiology, National Center Hospital of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Sato
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Fuyuko
authors.initials: F
authors.lastname: Yoshida
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Toshiya
authors.initials: T
authors.lastname: Teraishi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000328:Adult; D017487:Ankyrins / Q000235:genetics*; D001714:Bipolar Disorder / Q000000981:diagnostic imaging* / Q000235:genetics*; D001921:Brain / Q000000981:diagnostic imaging*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins
keywords: ankyrin 3; bipolar disorder; diffusion tensor imaging; tract-based spatial statistics; voxel-based morphometry