Ikuta T, Peters B D, Guha S, John M, Karlsgodt K H, Lencz T, Szeszko P R, Malhotra A K
Department of Communication Sciences and Disorders, School of Applied Sciences, University of Mississippi, University, MS, USA.
Division of Psychiatry Research, Zucker Hillside Hospital, Glen Oaks, NY, USA.
Schizophr Res. 2014 May;155(1-3):15-20. doi: 10.1016/j.schres.2014.03.001. Epub 2014 Mar 27.
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.
全基因组关联研究为锌指蛋白804A（ZNF804A）基因中的单核苷酸多态性（SNP）rs1344706与精神分裂症和双相情感障碍的关联提供了有力证据。神经影像学研究表明，rs1344706位点的变异可能与诸如白质体积和密度等神经内表型有关。然而，使用扩散张量成像（DTI）对白质微观结构进行的分析得出了相互矛盾的结果。我们使用基于束的空间统计学（TBSS）方法，在107名健康个体中研究了rs1344706与白质微观结构之间的关联。TBSS分析显示，风险等位基因与胼胝体、左侧小钳夹和右侧顶叶白质中较低的各向异性分数显著相关（p<0.05；FWE校正）。事后分析表明，这种关联主要由径向扩散率的改变驱动，这与基因型对髓鞘形成的影响一致。鉴于DTI有强有力的证据表明精神分裂症存在白质微观结构异常，目前的结果提示了ZNF804A rs1344706基因型导致精神分裂症风险形成的潜在机制。
