CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.
CNTNAP2 polymorphisms and structural brain connectivity: a diffusion-tensor imaging study.
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DOI：
10.1016/j.jpsychires.2013.07.002
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发表时间：
2013-10
影响因子：
4.8
通讯作者：
Mulert, Christoph
中科院分区：
文献类型：
--
作者：
von Hohenberg, Christian Clemm;Wigand, Marlene C.;Kubicki, Marek;Leicht, Gregor;Giegling, Ina;Karch, Susanne;Hartmann, Annette M.;Konte, Bettina;Friedl, Marion;Ballinger, Thomas;Eckbo, Ryan;Bouix, Sylvain;Jaeger, Lorenz;Shenton, Martha E.;Rujescu, Dan;Mulert, Christoph
CNTNAP2是7号染色体上的一个基因，与自闭症和精神分裂症有关，有证据表明它在神经元同步和大脑连接中起着重要作用。在这项研究中，我们评估了弥散张量成像（Diffusion Tensor Imaging， DTI）（一种假定的大脑解剖连接性标记）与分布在这个大基因上的多个单核苷酸多态性（snp）之间的关系。81名健康对照和44名精神分裂症患者（均为高加索人）进行了DTI和CNTNAP2内31个snp的基因分型。我们采用基于脑束的空间统计（TBSS）进行受试者间脑配准，并计算了6个主要白质束的平均扩散率值。计算协方差分析（ANCOVAs）来检验基因型之间可能存在的关联。在严格的Bonferroni校正中，rs2710126基因型与钩状束分数各向异性（FA）之间的相关性最强（p= 0.003）。考虑到CNTNAP2在发育中的大脑中丰富的额颞叶表达，这个解剖位置特别有趣。对于这个SNP，以前没有报道过表型关联。还有几个基因型- dti关联，名义上是显著的，但没有在Bonferroni校正中存活下来，包括背带束轴向扩散性与内含子13区域（由rs2710102、rs759178、rs2538991代表）之间的关联，该区域先前被报道与前后功能连接有关。我们提出了关于CNTNAP2对脑连通性影响的新证据，其破坏被假设为精神分裂症病理生理学的核心。
CNTNAP2 is a gene on chromosome 7 that has shown associations with autism and schizophrenia, and there is evidence that it plays an important role for neuronal synchronization and brain connectivity. In this study, we assessed the relationship between Diffusion Tensor Imaging (DTI), a putative marker of anatomical brain connectivity, and multiple single nucleotide polymorphisms (SNPs) spread out over this large gene. 81 healthy controls and 44 patients with schizophrenia (all Caucasian) underwent DTI and genotyping of 31 SNPs within CNTNAP2. We employed Tract-based Spatial Statistics (TBSS) for inter-subject brain registration and computed average diffusivity values for six major white matter tracts. Analyses of Covariance (ANCOVAs) were computed to test for possible associations with genotypes. The strongest association, which survived rigorous Bonferroni correction, was between rs2710126 genotype and Fractional Anisotropy (FA) in the uncinate fasciculus (p=.00003). This anatomical location is particularly interesting given the enriched fronto-temporal expression of CNTNAP2 in the developing brain. For this SNP, no phenotype association has been reported before. There were several further genotype-DTI associations that were nominally significant but did not survive Bonferroni correction, including an association between axial diffusivity in the dorsal cingulum bundle and a region in intron 13 (represented by rs2710102, rs759178, rs2538991), which has previously been reported to be associated with anterior-posterior functional connectivity. We present new evidence about the effects of CNTNAP2 on brain connectivity, whose disruption has been hypothesized to be central to schizophrenia pathophysiology.
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Klawiter, Eric C.;Schmidt, Robert E.;Trinkaus, Kathryn;Liang, Hsiao-Fang;Budde, Matthew D.;Naismith, Robert T.;Song, Sheng-Kwei;Cross, Anne H.;Benzinger, Tammie L.
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通讯作者：
Tesche CD