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

100K SNP 芯片上精神分裂症患者的全基因组关联研究。

基本信息

批准号：
18591321
负责人：
KAZUO Yamada
金额：
$ 2.49万
依托单位：
The Institute of Physical and Chemical Research
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591321/
关键词：
schizophrenia SNPChip linkage diseauilibrium genome gene SNPChip

项目摘要

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

全基因组关联分析（WGA）是一种潜在的强有力的手段，以确定复杂性状的共同变异。通过高通量SNP基因分型技术的快速发展，该技术的前景已成为现实。然而，对所得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显著性水平的小至中等效应等位基因。相反，少数真正的因果变量将被大量的假阳性关联所掩盖。因此，后续研究，如多阶段的方法是必要的，以区分少数真正的因果变异的高比例的假阳性associations.There，我们进行了三累阶段筛选，以确定精神分裂症的易感基因。对于第1层，使用Affymetrix基因芯片作图100K阵列对来自日本精神分裂症家系的120个三重样本进行基因分型。所有主题 ...更多信息 cts居住在日本中部。使用传递不平衡检验（TDT）评估家庭面板中的传递失真。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没有多态性，并从进一步的分析中排除。对于第2层，我们从第1层的结果中选择了1，536个SNP，并使用Illumina BeadArray技术成功地对日本病例对照样本（506个样本vs. 506个样本）中的1，496个SNP进行了基因分型。我们在第1层（P<0.01）和第2层（P<0.05）样本中确定了70个与日本精神分裂症相关的SNPs。第三层，对293个中国NIMH家系样本（1163人）进行了70个SNPs的验证性研究。我们的研究将为今后精神分裂症的遗传学研究提供有用的信息，通过跨人群独立复制的仔细论证将澄清精神分裂症发病机制的真正基因。少

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Linkage disequilibrium analysis of the CHRNA7 gene and its partially duplicated region in schizophrenia

DOI：
10.1016/j.neures.2006.10.002
发表时间：
2007-02-01
期刊：
NEUROSCIENCE RESEARCH
影响因子：
2.9
作者：
Iwata, Yasuhide;Nakajima, Mizuho;Collier, David
通讯作者：
Collier, David

Association between polymorphisms in the promoter region of the sialyltransferase 8B (SIAT8B) gene and schizophrenia

DOI：
10.1016/j.biopsych.2005.08.016
发表时间：
2006-04-01
期刊：
BIOLOGICAL PSYCHIATRY
影响因子：
10.6
作者：
Arai, M;Yamada, K;Itokawa, M
通讯作者：
Itokawa, M

Analysis of correlation between serum D-serine levels and functional promoter polymorphisms of GRIN2A and GRIN2B genes

DOI：
10.1016/j.neulet.2005.10.025
发表时间：
2006-02-13
期刊：
NEUROSCIENCE LETTERS
影响因子：
2.5
作者：
Iwayama, Y;Hashimoto, K;Yoshikawa, T
通讯作者：
Yoshikawa, T

Genetic analysis of the calcineurin pathway identifies members of the EGR gene family, specifically EGR3, as potential susceptibility candidates in schizophrenia

DOI：
10.1073/pnas.0610765104
发表时间：
2007-02-20
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子：
11.1
作者：
Yamada, Kazuo;Gerber, David J.;Yoshikawa, Takeo
通讯作者：
Yoshikawa, Takeo

Fabp7 maps to a quantitative trait locus for a shizophrenia endophenotype.

Fabp7 映射到精神分裂症内表型的数量性状基因座。