title: Effects of ANK3 variation on gray and white matter in bipolar disorder.
abstract: The single-nucleotide polymorphism rs9804190 in the Ankyrin G (ANK3) gene has been reported in genome-wide association studies to be associated with bipolar disorder (BD). However, the neural system effects of rs9804190 in BD are not known. We investigated associations between rs9804190 and gray and white matter (GM and WM, respectively) structure within a frontotemporal neural system implicated in BD. A total of 187 adolescent and adult European Americans were studied: a group homozygous for the C allele (52 individuals with BD and 56 controls) and a T-carrier group, carrying the high-risk T allele (38 BD and 41 controls). Subjects participated in high-resolution structural magnetic resonance imaging and diffusion tensor imaging (DTI) scanning. Frontotemporal region of interest (ROI) and whole-brain exploratory analyses were conducted. DTI ROI-based analysis revealed a significant diagnosis by genotype interaction within the uncinate fasciculus (P⩽0.05), with BD subjects carrying the T (risk) allele showing decreased fractional anisotropy compared with other subgroups, independent of age. Genotype effects were not observed in frontotemporal GM volume. These findings support effects of rs9804190 on frontotemporal WM in adolescents and adults with BD and suggest a mechanism contributing to WM pathology in BD.
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.|Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.
authors.forename: E T C
authors.initials: ETC
authors.lastname: Lippard
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.|Department of Psychiatry, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: K P
authors.initials: KP
authors.lastname: Jensen
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
authors.forename: F
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
authors.forename: J A Y
authors.initials: JAY
authors.lastname: Johnston
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
authors.forename: L
authors.initials: L
authors.lastname: Spencer
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
authors.forename: B
authors.initials: B
authors.lastname: Pittman
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.|Department of Psychiatry, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: J
authors.initials: J
authors.lastname: Gelernter
authors.affiliation: Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA.|Department of Radiology and Biomedical Imaging, Yale School of Medicine, New Haven, CT, USA.|Department of Psychiatry, VA Connecticut Healthcare System, West Haven, CT, USA.
authors.forename: H P
authors.initials: HP
authors.lastname: Blumberg
mesh_terms: D000293:Adolescent; D000328:Adult; D017487:Ankyrins / Q000235:genetics* / Q000378:metabolism; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D056324:Diffusion Tensor Imaging; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D066127:White Matter / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*
chemical_list: C490613:ANK3 protein, human; D017487:Ankyrins