a general model for multilocus epistatic interactions in case-control studies茎的通用模型上位相互作用的病例对照研究.pdfVIP

A General Model for Multilocus Epistatic Interactions in Case-Control Studies 1,2 3 4 4 4 1,2 Zhong Wang , Tian Liu , Zhenwu Lin , John Hegarty , Walter A. Koltun , Rongling Wu * 1 Center for Statistical Genetics, Pennsylvania State University, Hershey, Pennsylvania, United States of America, 2 Pennsylvania State Cancer Institute, Pennsylvania State University, Hershey, Pennsylvania, United States of America, 3 Human Genetics Group, Genome Institute of Singapore, Singapore, Singapore, 4 Department of Surgery, Pennsylvania State University, Hershey, Pennsylvania, United States of America Abstract Background: Epistasis, i.e., the interaction of alleles at different loci, is thought to play a central role in the formation and progression of complex diseases. The complexity of disease expression should arise from a complex network of epistatic interactions involving multiple genes. Methodology: We develop a general model for testing high-order epistatic interactions for a complex disease in a case- control study. We incorporate the quantitative genetic theory of high-order epistasis into the setting of cases and controls sampled from a natural population. The new model allows the identification and testing of epistasis and its various genetic components. Conclusions: Simulation studies were used to examine the power and false positive rates of the model under different sampling strategies. The model was used to detect epistasis in a case-control study of inflammatory bowel disease, in which five SNPs at a candidate gene were typed, leading to the identification of a significant three-locus epistasis. Citation: Wang Z, Liu T, Lin Z, Hegarty J, Koltun WA, et al. (2010) A General Model for Mul