Genome-wide association study of schizophrenic patients on 100K SNP Chip.

全基因组关联分析（WGA）是一种潜在的识别复杂性状基础的常见变异的强大手段。随着高通量SNP基因分型技术的快速发展，这一技术的前景已经成为现实。然而，对结果数据的解释需要非常小心，因为可能需要更大的样本量来检测具有高水平显著性的小到中等影响的等位基因。相反，少数真正的因果变异将被淹没在大量的假阳性关联中。因此，有必要进行后续研究，如多阶段方法，以区分少数真正的因果变异和高比例的假阳性关联。在这里，我们进行了三阶段筛选，以确定精神分裂症的易感基因。对于第一级，使用AffymetrixGeneChip Mapping 100K阵列对来自日本精神分裂症谱系的120个三人样本进行基因分型。所有受试者…更多的受试者居住在日本中部。使用传输不平衡测试（TDT）评估家庭面板中的传输畸变。我们对115,700个SNP标记进行了基因分型，其中17,807个SNP在我们的日本样本中不具有多态性，并被排除在进一步的分析之外。对于第2层，我们从第1层的结果中选择了1536个snp，并利用illumina BeadArray技术成功地在日本病例对照样本（506个样本对506个样本）中对1496个snp进行了基因分型。我们在一级（P<0.01）和二级（P<0.05）样本中发现了70个与日本精神分裂症相关的snp。第三层，对293份NIMH中国家系样本（1163人）进行70个snp的确证研究。在这项研究中，我们代表了鉴定精神分裂症易感基因的多阶段方法。我们的研究将为未来精神分裂症的遗传研究提供有用的信息，并且通过在人群中独立复制的仔细证明将澄清导致精神分裂症发病机制的真正基因。少

Whole genome association analysis (WGA) is a potentially powerful means of identifying the common variants that underlie complex traits. The promise of this technique has become a reality through the rapid development of high-throughput SNP genotyping technology. However, interpretation of the resulting data requires great care, since larger sample sizes may be required to detect small-to-modest effect alleles with high level of significance. Conversely, a small number of genuine causal variants will be buried within a larger number of false-positive associations. Therefore, follow-up studies such as multi-stage approaches are necessary to distinguish the small number of genuine causal variants from the high proportion of false-positive associations.Here, we performed a three-tired stage screening to identify susceptibility genes for schizophrenia. For tier 1, 120 trio samples from Japanese schizophrenic pedigrees were genotyped using-an AffymetrixGeneChip Mapping 100K Array. All subje … More cts resided in central Japan. Transmission distortions in the family panel were evaluated using the transmission disequilibrium test (TDT). We genotyped 115, 700 SNP markers, of which 17, 807 SNPs were not polymorphic in our Japanese samples and excluded from further analyses. For tier 2, we selected 1, 536 SNPs from the result of tire 1, and successfully genotyped 1, 496 SNPs in Japanese case-control samples (506 samples vs. 506 samples) by using illumina BeadArray technology. We identified 70 SNPs that were associated with Japanese schizophrenia in both tier 1 (P<0.01) and tier 2 (P<0.05) samples. For tier 3, confirmation study for 70 SNPs was performed by 293 NIMH Chinese pedigree samples (1, 163 individuals).In this study, we represent the multi-stage approaches to identify susceptibility genes for schizophrenia. Our study will provide useful information for the future genetic study of schizophrenia, and careful justification by independent replication across population will clarify the genuine genes that contribute to the pathogenesis of schizophrenia. Less