Haplotype-Based Pharmacogenetic Analysis for Longitudinal Quantitative Traits in the Presence of Dropout

被引:3
作者
Tzeng, Jung-Ying [1 ]
Lu, Wenbin [1 ]
Farmen, Mark W. [2 ]
Liu, Youfang [3 ]
Sullivan, Patrick F. [3 ]
机构
[1] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA
[2] Eli Lilly & Co, Dept Stat, Indianapolis, IN 46285 USA
[3] Univ N Carolina, Dept Genet Psychiat & Epidemiol, Chapel Hill, NC USA
关键词
Adaptive LASSO; Haplotype-based association analysis; Haplotype-treatment interaction; Missing data; Repeated outcome; Variable selection; SCHIZOPHRENIA; LASSO; CATIE;
D O I
10.1080/10543400903572787
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
We propose a variety of methods based on the generalized estimation equations to address the issues encountered in haplotype-based pharmacogenetic analysis, including analysis of longitudinal data with outcome-dependent dropouts, and evaluation of the high-dimensional haplotype and haplotype-drug interaction effects in an overall manner. We use the inverse probability weights to handle the outcome-dependent dropouts under the missing-at-random assumption, and incorporate the weighted L1 penalty to select important main and interaction effects with high dimensionality. The proposed methods are easy to implement, computationally efficient, and provide an optimal balance between false positives and false negatives in detecting genetic effects.
引用
收藏
页码:334 / 350
页数:17
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