An entropy-based approach for testing genetic epistasis underlying complex diseases

doi:10.1016/j.jtbi.2007.10.001

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	An entropy-based approach for testing genetic epistasis underlying complex diseases
	Kang, Guolian 2; Yue, Weihua 1; Zhang, Jifeng3 ; Cui, Yuehua 2; Zuo, Yijun 2; Zhang, Dai 1
刊名	JOURNAL OF THEORETICAL BIOLOGY
	2008-01-21
卷号	250 期号:2 页码:362-374
关键词	case-only design complex diseases entropy genetic epistasis genetic network
ISSN号	0022-5193
DOI	10.1016/j.jtbi.2007.10.001
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.
WOS研究方向	Life Sciences & Biomedicine - Other Topics ; Mathematical & Computational Biology
语种	英语
出版者	ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
WOS记录号	WOS:000253003900012
内容类型	期刊论文
源URL	[http://ir.amss.ac.cn/handle/2S8OKBNM/6748]
专题	系统科学研究所
通讯作者	Zhang, Dai
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
推荐引用方式 GB/T 7714	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.