Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations
Identifying potential risk haplotypes for schizophrenia at the DTNBP1 locus in Han Chinese and Scottish populations
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DOI：
10.1038/sj.mp.4001718
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发表时间：
2005-11-01
影响因子：
11
通讯作者：
Collier, DA
中科院分区：
文献类型：
--
作者：
Li, T;Zhang, F;Collier, DA
染色体6p上的营养不良蛋白结合蛋白1(DTNBP1)基因已成为精神分裂症的潜在易感基因。虽然复制原始关联发现的一些尝试已经成功，但他们还没有发现任何明显的致病变异或所有研究人群共同的单一风险单倍型。在本研究中，我们试图在四川省汉族人口中国的638个核心家庭的独立样本中进一步复制。我们还检查了580例苏格兰精神分裂症患者和620名对照组。我们对最初的关联报告中使用的DTNBP1中的10个单核苷酸多态(SNPs)以及可能与精神分裂症相关的启动子区域的rs2619538(SNP‘A’)进行了基因分型。在这三个中国人中，我们发现两个SNPs(P1635和P1765)被显著地过度传播，但其等位基因与原始研究中报道的相反。SNPs P1757和P1765形成共同的单倍型，也表现出显著的超传。在苏格兰病例和对照组中，没有单独的标志物与精神分裂症显著相关。单个单倍型(包括rs2619538和P1583)和一个罕见单倍型(包括P1320和P1757)与精神分裂症显著相关，但以前没有报道过单倍型与精神分裂症相关。基于中国人群的数据，我们的结果为DTNBP1作为精神分裂症的易感基因提供了统计支持，尽管其单倍型与原始研究的不同。然而，我们在苏格兰样本中缺乏重复也表明，在评估DTNBP1作为精神分裂症遗传危险因素的证据的稳健性时，有必要谨慎行事。
The dystrobrevin-binding protein 1 (DTNBP1) gene on chromosome 6p has emerged as a potential susceptibility gene for schizophrenia. Although a number of attempts to replicate the original association finding have been successful, they have not identified any obvious pathogenic variants or a single at risk haplotype common to all populations studied. In the present study we attempted further replication in an independent sample of 638 nuclear families from the Han Chinese population of Sichuan Province, SW China. We also examined 580 Scottish schizophrenic cases and 620 controls. We genotyped 10 single-nucleotide polymorphisms ( SNPs) in DTNBP1 that were used in the original report of association, plus rs2619538 ( SNP 'A') in the putative promoter region, which has also been associated with schizophrenia. In the Chinese trios we found that two SNPs (P1635 and P1765) were significantly overtransmitted, but with alleles opposite to those reported in the original studies. SNPs P1757 and P1765 formed a common haplotype, which also showed significant overtransmission. In the Scottish cases and controls, no individual markers were significantly associated with schizophrenia. A single haplotype, which included rs2619538 and P1583, and one rare haplotype, composed of P1320 and P1757, were significantly associated with schizophrenia, but no previously reported haplotypes were associated. Based on the data from the Chinese population, our results provide statistical support for DTNBP1 as a susceptibility gene for schizophrenia, albeit with haplotypes different from those of the original study. However, our lack of replication in the Scottish samples also indicates that caution is warranted when evaluating the robustness of the evidence for DTNBP1 as genetic risk factor for schizophrenia.