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

作者：Kang Guolian; Yue Weihua; Zhang Jifeng; Cui Yuehua; Zuo Yijun; Zhang Dai^*

来源：Journal of Theoretical Biology, 2008, 250(2): 362-374.

DOI：10.1016/j.jtbi.2007.10.001

• case-only design
• complex diseases
• entropy
• genetic epistasis
• genetic network

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.

• 出版日期2008-1-21
• 单位北京大学; 中国科学院数学与系统科学研究院