Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample
Failure to replicate the association between NRG1 and schizophrenia using Japanese large sample
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DOI：
10.1016/j.schres.2008.01.010
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发表时间：
2008-04-01
影响因子：
4.5
通讯作者：
Iwata, Nakao
中科院分区：
文献类型：
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作者：
Ikeda, Masashi;Takahashi, Nagahide;Iwata, Nakao
冰岛人群中8p12-21的系统连锁不平衡（LD）定位确定了神经调节蛋白1 （NRG1）作为精神分裂症的pdrne候选基因。然而，重复性研究的结果并不一致，也没有大样本分析的报道。因此，我们设计了这项研究，目的是在日本人群中使用基于基因的关联方法来评估精神分裂症与NRG1（特别是HAP（ICE）区域和外显子区域）之间的推定关联。本研究采用两阶段关联分析方法，对不同的样本进行分析，其中在第一组筛选样本（1126例病例和1022例对照）中发现的显著相关性在确认样本（1262例病例和1172例对照，以及166例三人样本）中进一步评估。在第一组扫描中，检测了60个snp（49个来自HapMap数据库的标记snp， 4个来自其他论文的snp， 7个在突变扫描中检测到的snp）。一个单倍型在第一组筛选样本中显示出显著的相关性（全局p值= 0.0244，未经校正）。然而，我们无法在以下独立的确认样本中复制这种关联。此外，通过从HapMap数据库中输入未基因分型的snp，我们没有找到足够的证据证明在第一组样本中确定的单倍型存在显著的关联。这些结果表明NRG1的位置和功能吸引区域不太可能导致日本人群对精神分裂症的易感性。此外，我们的结果的性质支持大样本量的两阶段分析适合于检查常见疾病的易感基因。(C) 2008 Elsevier B.V.版权所有
Systematic linkage disequilibrium (LD) mapping of 8p12-21 in the Icelandic population identified neuregulin 1 (NRG1) as a pdrne candidate gene for schizophrenia. However, results of replication studies have been inconsistent, and no large sample analyses have been reported. Therefore, we designed this study with the aim of assessing this putative association between schizophrenia and NRG1 (especially HAP(ICE) region and exon region) using a gene-based association approach in the Japanese population.This study was a two-stage association analysis with a different panel of samples, in which the significant association found in the first-set screening samples (1126 cases and 1022 controls) was further assessed in the confirmation samples (1262 cases and 1172 controls, and 166 trio samples). In the first-set scan, 60 SNPs (49 tagging SNPs from HapMap database, four SNPs from other papers, and seven SNPs detected in the mutation scan) were examined.One haplotype showed a significant association in the first-set screening samples (Global P-value= 0.0244, uncorrected). However, we could not replicate this association in the following independent confirmation samples. Moreover, we could not find sufficient evidence for association of the haplotype identified as being significant in the first-set samples by imputing ungenotyped SNPs from HapMap database.These results indicate that the positionally and functionally attractive regions of NRG1 are unlikely to contribute to susceptibility to schizophrenia in the Japanese population. Moreover, the nature of our results support that two-stage analysis with large sample size is appropriate to examine the susceptibility genes for common diseases. (C) 2008 Elsevier B.V. All rights reserved.