Genome-Wide Association Study of Schizophrenia in a Japanese Population
Genome-Wide Association Study of Schizophrenia in a Japanese Population
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DOI：
10.1016/j.biopsych.2010.07.010
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发表时间：
2011-03-01
影响因子：
10.6
通讯作者：
Iwata, Nakao
中科院分区：
文献类型：
--
作者：
Ikeda, Masashi;Aleksic, Branko;Iwata, Nakao
背景：全基因组关联研究已经发现了少量弱但强有力支持的精神分裂症风险等位基因。此外，大量的多基因组成的障碍，包括大量的这样的等位基因已被报道的国际Schizophrenia Consortium.Method：我们报告了日本的全基因组关联研究精神分裂症，包括575例和564对照。我们试图复制97个标记，代表一个非冗余的面板标记主要来自前150名的发现，在多达三个数据集，共1990例和5389对照。然后，我们试图在日本人中复制对该疾病的多基因成分的观察，并确定这是否与英国人群中观察到的重叠。单位点分析没有揭示全基因组关联研究样本中任何位点的全基因组支持（最佳p = 6.2 x 10（-6））或在最佳支持基因座为SULT 6 B1的完整数据集中（rs 11895771：荟萃分析中p = 3.7 x 10（-5））。在以前由全基因组关联研究支持的基因座中，我们获得了日本对NOTCH 4的支持（rs 2071287：p（Meta）= 5.1 x 10（-5））。使用国际精神分裂症协会报告的方法，我们在日本人群中复制了精神分裂症多基因成分的观察结果（p = .005）。我们的跨日本-英国精神分裂症的分析也揭示了一个显着的相关性（最好的p = 7.0 × 10（-5）），在多基因组件across population.Conclusions：这些结果表明，精神分裂症的共享多基因风险之间的日本人和高加索人的样本，虽然我们没有发现明确的证据，一个新的易感基因精神分裂症。
Background: Genome-wide association studies have detected a small number of weak but strongly supported schizophrenia risk alleles. Moreover, a substantial polygenic component to the disorder consisting of a large number of such alleles has been reported by the International Schizophrenia Consortium.Method: We report a Japanese genome-wide association study of schizophrenia comprising 575 cases and 564 controls. We attempted to replicate 97 markers, representing a nonredundant panel of markers derived mainly from the top 150 findings, in up to three data sets totaling 1990 cases and 5389 controls. We then attempted to replicate the observation of a polygenic component to the disorder in the Japanese and to determine whether this overlaps that seen in UK populations.Results: Single-locus analysis did not reveal genome-wide support for any locus in the genome-wide association study sample (best p = 6.2 x 10(-6)) or in the complete data set in which the best supported locus was SULT6B1 (rs11895771: p = 3.7 x 10(-5) in the meta-analysis). Of loci previously supported by genome-wide association studies, we obtained in the Japanese support for NOTCH4 (rs2071287: p(meta) = 5.1 x 10(-5)). Using the approach reported by the International Schizophrenia Consortium, we replicated the observation of a polygenic component to schizophrenia within the Japanese population (p = .005). Our trans Japan-UK analysis of schizophrenia also revealed a significant correlation (best p = 7.0 x 10(-5)) in the polygenic component across populations.Conclusions: These results indicate a shared polygenic risk of schizophrenia between Japanese and Caucasian samples, although we did not detect unequivocal evidence for a novel susceptibility gene for schizophrenia.