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An entropy-based approach for testing genetic epistasis underlying complex diseases
Kang, Guolian2; Yue, Weihua1; Zhang, Jifeng3; Cui, Yuehua2; Zuo, Yijun2; Zhang, Dai1
关键词case-only design complex diseases entropy genetic epistasis genetic network
刊名JOURNAL OF THEORETICAL BIOLOGY
2008-01-21
DOI10.1016/j.jtbi.2007.10.001
250期:2页:362-374
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biology ; Mathematical & Computational Biology
研究领域[WOS]Life Sciences & Biomedicine - Other Topics ; Mathematical & Computational Biology
关键词[WOS]GENOME-WIDE ASSOCIATION ; SCHIZOPHRENIA GENES ; JOINT ANALYSIS ; POLYMORPHISMS ; EXPRESSION ; YEAST
英文摘要

The genetic basis of complex diseases is expected to be highly heterogeneous, with complex interactions among multiple disease loci and environment factors. Due to the multi-dimensional property of interactions among large number of genetic loci, efficient statistical approach has not been well developed to handle the high-order epistatic complexity. In this article, we introduce a new approach for testing genetic epistasis in multiple loci using an entropy-based statistic for a case-only design. The entropy-based statistic asymptotically follows a chi(2) distribution. Computer simulations show that the entropy-based approach has better control of type I error and higher power compared to the standard chi(2) test. Motivated by a schizophrenia data set, we propose a method for measuring and testing the relative entropy of a clinical phenotype, through which one can test the contribution or interaction of multiple disease loci to a clinical phenotype. A sequential forward selection procedure is proposed to construct a genetic interaction network which is illustrated through a tree-based diagram. The network information clearly shows the relative importance of a set of genetic loci on a clinical phenotype. To show the utility of the new entropy-based approach, it is applied to analyze two real data sets, a schizophrenia data set and a published malaria data set. Our approach provides a fast and testable framework for genetic epistasis study in a case-only design. (c) 2007 Elsevier Ltd. All rights reserved.

语种英语
WOS记录号WOS:000253003900012
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被引频次:39[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59204
专题北京大学精神卫生研究所
北京大学第一临床医学院_妇产科
北京大学精神卫生研究所_精神科
作者单位1.Peking Univ, Inst Mental Hlth, Minist Hlth, Key Lab Mental Hlth, Beijing 100083, Peoples R China
2.Michigan State Univ, Dept Stat & Probabil, E Lansing, MI 48824 USA
3.Chinese Acad Sci, Acad Math & Syst Sci, Inst Syst Sci, Beijing 100080, Peoples R China
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Kang, Guolian,Yue, Weihua,Zhang, Jifeng,et al. An entropy-based approach for testing genetic epistasis underlying complex diseases[J]. JOURNAL OF THEORETICAL BIOLOGY,2008,250(2):362-374.
APA Kang, Guolian,Yue, Weihua,Zhang, Jifeng,Cui, Yuehua,Zuo, Yijun,&Zhang, Dai.(2008).An entropy-based approach for testing genetic epistasis underlying complex diseases.JOURNAL OF THEORETICAL BIOLOGY,250(2),362-374.
MLA Kang, Guolian,et al."An entropy-based approach for testing genetic epistasis underlying complex diseases".JOURNAL OF THEORETICAL BIOLOGY 250.2(2008):362-374.
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