A comprehensive approach to haplotype-specific analysis by penalized likelihood.
Haplotypes can hold key information to understand the role of candidate genes in disease etiology. However, standard haplotype analysis has yet been able to fully reveal the information retained by haplotypes. In most analysis, haplotype inference focuses on relative effects compared with an arbitrarily chosen baseline haplotype. It does not depict the effect structure unless an additional inference procedure is used in a secondary post hoc analysis, and such analysis tends to be lack of power. In this study, we propose a penalized regression approach to systematically evaluate the pattern and structure of the haplotype effects. By specifying an L1 penalty on the pairwise difference of the haplotype effects, we present a model-based haplotype analysis to detect and to characterize the haplotypic association signals. The proposed method avoids the need to choose a baseline haplotype; it simultaneously carries out the effect estimation and effect comparison of all haplotypes, and outputs the haplotype group structure based on their effect size. Finally, our penalty weights are theoretically designed to balance the likelihood and the penalty term in an appropriate manner. The proposed method can be used as a tool to comprehend candidate regions identified from a genome or chromosomal scan. Simulation studies reveal the better abilities of the proposed method to identify the haplotype effect structure compared with the traditional haplotype association methods, demonstrating the informativeness and powerfulness of the proposed method.
Tzeng
Jung-Ying
JY
Department of Statistics, North Carolina State University, Campus Box 7566, Raleigh NC 27695, USA. jytzeng@stat.ncsu.edu
Bondell
Howard D
HD
D003198:Computer Simulation; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D016013:Likelihood Functions; D015233:Models, Statistical; D019655:Quantitative Trait, Heritable