A schizophrenia risk gene, ZNF804A , is associated with brain white matter microstructure

• Published in: Schizophrenia research Vol. 155; no. 1; pp. 15 - 20
• Main Authors: Ikuta, T, Peters, B.D, Guha, S, John, M, Karlsgodt, K.H, Lencz, T, Szeszko, P.R, Malhotra, A.K
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.05.2014; Elsevier
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Aged; Anisotropy; Biological and medical sciences; Brain - anatomy & histology; Child; Diffusion Magnetic Resonance Imaging; Diffusion tensor imaging; Endophenotype; Female; Functional Laterality - genetics; Gene Frequency; Genetic Association Studies; Genetics; Genotype; Humans; Kruppel-Like Transcription Factors - genetics; Male; Medical sciences; Middle Aged; Polymorphism, Single Nucleotide - genetics; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Schizophrenia; Schizophrenia - genetics; White matter; White Matter - anatomy & histology; Young Adult; ZNF804A; Schizophrenia; ZNF804A; Genetics; White matter; Endophenotype; Diffusion tensor imaging; Human; Central nervous system; Genetic determinism; Nuclear magnetic resonance imaging; Encephalon; Psychosis; Gene; Medical imagery
• ISSN: 0920-9964; 1573-2509
• DOI: 10.1016/j.schres.2014.03.001

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.