title: Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations.
abstract: The rs1344706 single nucleotide polymorphism within intron 2 of the ZNF804A gene is strongly associated with schizophrenia and bipolar disorder. This variant has also been associated in some studies with a range of cognitive and neuroimaging phenotypes, but several studies have reported no effect on the same phenotypes in other samples. Here, we genotyped 670 healthy adult Norwegian subjects and 1753 healthy adult Swedish subjects for rs1344706, and tested for associations with cognitive phenotypes including general intellectual abilities, memory functions and cognitive inhibition. We also tested whether rs1344706 is associated with white matter microstructural properties using diffusion tensor imaging (DTI) data from 250 to 340 of the Norwegian and Swedish subjects, respectively. Whole-brain voxel-wise statistical modeling of the effect of the ZNF804A variant on two DTI indices, fractional anisotropy (FA) and radial diffusivity (RD), was performed using tract-based spatial statistics (TBSS), and commonly reported effect sizes were calculated within several large-scale white matter pathways based on neuroanatomical atlases. No significant associations were found between rs1344706 and the cognitive traits or white matter microstructure. We conclude that the rs1344706 SNP has no significant effect on these phenotypes in our two reasonably powered samples.
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway; K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Carla Patricia Duarte
authors.initials: CP
authors.lastname: Fernandes
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo N-0317, Norway.
authors.forename: Lars Tjelta
authors.initials: LT
authors.lastname: Westlye
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Sudheer
authors.initials: S
authors.lastname: Giddaluru
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Andrea
authors.initials: A
authors.lastname: Christoforou
authors.affiliation: Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
authors.forename: Karolina
authors.initials: K
authors.lastname: Kauppi
authors.affiliation: Department of Clinical Sciences, Division of Psychiatry, Umeå University, Umeå, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Adolfsson
authors.affiliation: Department of Psychology, Stockholm University and Stockholm Brain Institute, Uppsala, Sweden.
authors.forename: Lars-Göran
authors.initials: LG
authors.lastname: Nilsson
authors.affiliation: Umeå Center for Functional Brain Imaging, Department of Integrative Medical Biology, Physiology Section, and Department of Radiation Sciences, Diagnostic Radiology, Umeå University, Umeå, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Nyberg
authors.affiliation: Department of Biological and Medical Psychology, University of Bergen, Bergen, Norway; Kavli Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway; K.G. Jebsen Centre for Research on Neuropsychiatric Disorders, University of Bergen, Bergen, Norway.
authors.forename: Astri Johansen
authors.initials: AJ
authors.lastname: Lundervold
authors.affiliation: Department of Psychology, University of Oslo, Oslo N-0317, Norway.
authors.forename: Ivar
authors.initials: I
authors.lastname: Reinvang
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Vidar Martin
authors.initials: VM
authors.lastname: Steen
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Norwegian Centre for Mental Disorders Research (NORMENT), Department of Clinical Science, University of Bergen, Bergen, Norway; Dr. Einar Martens Research Group for Biological Psychiatry, Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Le Hellard
authors.affiliation: K.G. Jebsen Centre for Psychosis Research, Norwegian Centre For Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Psychology, University of Oslo, Oslo N-0317, Norway. Electronic address: thomas.espeseth@psykologi.uio.no.
authors.forename: Thomas
authors.initials: T
authors.lastname: Espeseth
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016880:Anisotropy; D001369:Axons / Q000502:physiology; D001921:Brain / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D056324:Diffusion Tensor Imaging; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007266:Inhibition, Psychological; D007360:Intelligence / Q000502:physiology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D059906:Neuroimaging; D009664:Norway; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D013548:Sweden; D055815:Young Adult
chemical_list: D051741:Kruppel-Like Transcription Factors; C540527:ZNF804A protein, human
keywords: Fractional anisotropy; Neuroimaging; Radial diffusivity