Haplotype-based pharmacogenetic analysis for longitudinal quantitative traits in the presence of dropout

J Biopharm Stat. 2010 Mar;20(2):334-50. doi: 10.1080/10543400903572787.

Abstract

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 L(1) 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antipsychotic Agents / therapeutic use
  • Computer Simulation
  • Data Interpretation, Statistical
  • Genetic Predisposition to Disease
  • Haplotypes
  • Humans
  • Likelihood Functions
  • Longitudinal Studies
  • Models, Statistical*
  • Patient Dropouts / statistics & numerical data*
  • Pharmacogenetics / statistics & numerical data*
  • Phenotype
  • Quantitative Trait, Heritable*
  • Randomized Controlled Trials as Topic / statistics & numerical data*
  • Reproducibility of Results
  • Schizophrenia / drug therapy
  • Schizophrenia / genetics
  • Treatment Outcome

Substances

  • Antipsychotic Agents