Association of neuregulin 1 with schizophrenia confirmed in a Scottish population
Association of neuregulin 1 with schizophrenia confirmed in a Scottish population
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DOI：
10.1086/345442
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发表时间：
2003-01-01
影响因子：
9.8
通讯作者：
St Clair, D
中科院分区：
文献类型：
--
作者：
Stefansson, H;Sarginson, J;St Clair, D
最近，我们通过联合连锁和关联方法，确定了神经调节蛋白1 （NRG1）是冰岛人群中精神分裂症的易感基因。在这里，我们报告了第一项评估NRG1与冰岛以外人群精神分裂症相关性的研究。在冰岛人NRG1基因5'端发现的代表核心风险单倍型的标记物在609名无血缘关系的苏格兰患者和618名无血缘关系的苏格兰对照个体中进行了基因分型。该单倍型由5个SNP标记和2个微卫星组成，它们都表现出强烈的连锁不平衡。对于苏格兰患者和对照组，单倍型频率使用最大似然估计，使用期望最大化算法。7标记单倍型在苏格兰患者中的频率显著高于对照组（10.2% vs. 5.9%, P = 0.00031）。估计风险比为1.8，这与我们报道的冰岛无血缘关系患者（2.1）一致。单倍型的7个标记中有3个给出了单点P值，范围从。000064年。0021为高危单倍型的等位基因。这种单倍型关联在第二群体中的直接复制进一步暗示NRG1是导致精神分裂症病因的一个因素。
Recently, we identified neuregulin 1 (NRG1) as a susceptibility gene for schizophrenia in the Icelandic population, by a combined linkage and association approach. Here, we report the first study evaluating the relevance of NRG1 to schizophrenia in a population outside Iceland. Markers representing a core at-risk haplotype found in Icelanders at the 5' end of the NRG1 gene were genotyped in 609 unrelated Scottish patients and 618 unrelated Scottish control individuals. This haplotype consisted of five SNP markers and two microsatellites, which all appear to be in strong linkage disequilibrium. For the Scottish patients and control subjects, haplotype frequencies were estimated by maximum likelihood, using the expectation-maximization algorithm. The frequency of the seven-marker haplotype among the Scottish patients was significantly greater than that among the control subjects (10.2% vs. 5.9%, P = .00031). The estimated risk ratio was 1.8, which is in keeping with our report of unrelated Icelandic patients (2.1). Three of the seven markers in the haplotype gave single-point P values ranging from .000064 to.0021 for the allele contributing to the at-risk haplotype. This direct replication of haplotype association in a second population further implicates NRG1 as a factor that contributes to the etiology of schizophrenia.