• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Gene-gene interaction and gene-pathway analysis of genome-wide association for schizophrenia.
【24h】

Gene-gene interaction and gene-pathway analysis of genome-wide association for schizophrenia.

机译：精神分裂症的全基因组关联的基因-基因相互作用和基因-途径分析。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Schizophrenia (SZ) is a complex disorder with high heritability and variable phenotypes that has limited success in finding causal genes associated with the disease development. Pathway-based analysis is an effective approach in investigating the molecular mechanism of susceptible genes associated with complex diseases. The etiology of complex diseases could be a network of genetic factors and within the genes, interaction may occur. In this work we argue that some genes might be of small effect that by itself are neither sufficient nor necessary to cause the disease however, their effect may induce slight changes to the gene expression or affect the protein function, therefore, analyzing the gene-gene interaction mechanism within the disease pathway would play crucial role in dissecting the genetic architecture of complex diseases, making the pathway-based analysis a complementary approach to GWAS technique.;In this study, we implemented three novel linkage disequilibrium based statistics, the linear combination, the quadratic, and the decorrelation test statistics, to investigate the interaction between linked and unlinked genes in two independent case-control GWAS datasets for SZ including participants of European (EA) and African (AA) ancestries. The EA population included 1,173 cases and 1,378 controls with 729,454 genotyped SNPs, while the AA population included 219 cases and 288 controls with 845,814 genotyped SNPs. We identified 17,186 interacting gene-sets at significant level in EA dataset, and 12,691 gene-sets in AA dataset using the gene-gene interaction method. We also identified 18,846 genes in EA dataset and 19,431 genes in AA dataset that were in the disease pathways. However, few genes were reported of significant association to SZ.;Our research determined the pathways characteristics for schizophrenia through the gene-gene interaction and gene-pathway based approaches. Our findings suggest insightful inferences of our methods in studying the molecular mechanisms of common complex diseases.
机译：精神分裂症（SZ）是一种具有高遗传力和可变表型的复杂疾病，在发现与疾病发展相关的因果基因方面取得的成功有限。基于途径的分析是研究与复杂疾病相关的易感基因的分子机制的有效方法。复杂疾病的病因可能是遗传因素的网络，并且在基因内可能发生相互作用。在这项工作中，我们认为某些基因可能效果不大，仅靠它们本身不足以引起疾病，但它们的作用可能导致基因表达略有变化或影响蛋白质功能，因此，对基因进行分析疾病途径内的相互作用机制将在剖析复杂疾病的遗传结构中发挥关键作用，使基于途径的分析成为GWAS技术的补充方法。在本研究中，我们实现了三种新颖的基于连锁不平衡的统计数据，即线性组合，二次方和去相关检验统计量，以调查SZ的两个独立的病例对照GWAS数据集中链接和未链接的基因之间的相互作用，包括欧洲（EA）和非洲（AA）祖先的参与者。 EA人群包括1,173例病例和1,378例具有729,454个基因型SNP的对照，而AA人群包括219例病例和288例具有845,814种基因型的SNP。我们使用基因-基因相互作用方法在EA数据集中确定了17,186个相互作用的基因集，而在AA数据集中则确定了12,691个相互作用的基因集。我们还确定了EA数据集中的18,846个基因和AA数据集中的19,431个基因，这些基因均位于疾病途径中。然而，几乎没有报道与SZ有显着关联的基因。我们的研究通过基因-基因相互作用和基于基因-途径的方法确定了精神分裂症的途径特征。我们的发现暗示了我们研究常见复杂疾病分子机制的方法的深刻见解。

著录项

  • 作者

    Nassar, Aaya M.;

  • 作者单位

    The University of Texas School of Public Health.;

  • 授予单位 The University of Texas School of Public Health.;
  • 学科 Health Sciences Epidemiology.;Biology Genetics.;Biology Biostatistics.
  • 学位 Ph.D.
  • 年度 2012
  • 页码 224 p.
  • 总页数 224
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号