Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia
Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia
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DOI：
10.1016/j.neures.2006.10.002
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发表时间：
2007-02-01
影响因子：
2.9
通讯作者：
Collier, David
中科院分区：
文献类型：
--
作者：
Iwata, Yasuhide;Nakajima, Mizuho;Collier, David
先前的几项研究报道了 α7 烟碱胆碱能受体亚基 (CHRNA7) 基因中的标记与精神分裂症或 P50 感觉门控缺陷（一种精神分裂症内表型）之间的显着联系。然而，CHRFAM7A（CHRNA 7 基因上游 1.6 Mb 的部分复制基因）使进一步的遗传分析变得复杂。我们对 188 名无血缘关系的中国汉族精神分裂症患者和 188 名对照者的全长 CHRNA 7 基因和重复区域的 14 个多态性标记进行了基因分型。通过对每个区域附近的上游和下游多态性标记进行基因分型并分析每对标记之间的连锁不平衡（LD）来评估重复区域。 LD 分析中未发现 CHRNA7 基因或部分重复区域存在精神分裂症风险变异的证据。仅在患者的 SNP9 (IVS4-1912) 基因型分布中发现与 Hardy-Weinberg 平衡 (HWE) 的显着偏差 (p = 0.00829)，但在对照中未发现。总之，我们的 LD 分析没有揭示中国汉族人群中的精神分裂症与 CHRNA7 基因或其部分重复区域之间的任何关联。然而，由于样本量较小，我们不能排除遗传效应较弱的可能性。仍然需要对更大的样本和更高密度的标记进行分析，特别是围绕 SNP9 (IVS4-1912)。 (c) 2006 Elsevier Ireland Ltd 和日本神经科学学会。版权所有。
Several previous studies have reported a significant linkage between markers in the alpha 7 nicotinic cholinergic receptor subunit (CHRNA7) gene and either schizophrenia or the P50 sensory gating deficit, a schizophrenia endophenotype. However, CHRFAM7A, a partially duplicated gene 1.6 Mb upstream of the CHRNA 7 gene, has complicated further genetic analysis. We genotyped 14 polymorphic markers throughout the full-length CHRNA 7 gene and the duplicated region in 188 unrelated Han Chinese patients with schizophrenia and 188 controls. The duplicated regions were assessed by genotyping up- and down-stream polymorphic markers in the vicinity of each region and analyzing the linkage disequilibrium (LD) between each pair of markers. No evidence of risk variants for schizophrenia in either the CHRNA7 gene or the partially duplicated region was found in the LD analysis. A significant deviation from the Hardy-Weinberg equilibrium (HWE) was found only in the genotypic distribution of SNP9 (IVS4-1912) in patients (p = 0.00829), but not in controls. In conclusion, our LD analysis did not reveal any association between schizophrenia in our Han Chinese population and the CHRNA7 gene or its partially duplicated region. However, we could not exclude the possibility of a weak genetic effect due to the small sample size. Analyses of larger samples and higher-density markers, particularly around SNP9 (IVS4-1912), are still needed. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.