Shrinkage estimators for robust and efficient inference in haplotype-based case-control studies

Yi Hau Chen, Nilanjan Chatterjee, Raymond J. Carroll

Research output: Contribution to journalArticle

Abstract

Case-control association studies often aim to investigate the role of genes and gene-environment interactions in terms of the underlying haplotypes (i.e., the combinations of alleles at multiple genetic loci along chromosomal regions). The goal of this article is to develop robust but efficient approaches to the estimation of disease odds-ratio parameters associated with haplotypes and haplotype-environment interactions. We consider "shrinkage" estimation techniques that can adaptively relax the model assumptions of Hardy-Weinberg-Equilibrium and gene-environment independence required by recently proposed efficient "retrospective" methods. Our proposal involves first development of a novel retrospective approach to the analysis of case-control data, one that is robust to the nature of the gene-environment distribution in the underlying population. Next, it involves shrinkage of the robust retrospective estimator toward a more precise, but model dependent, retrospective estimator using novel empirical Bayes and penalized regression techniques. Methods for variance estimation are proposed based on asymptotic theories. Simulations and two data examples illustrate both the robustness and efficiency of the proposed methods.

Original languageEnglish (US)
Pages (from-to)220-233
Number of pages14
JournalJournal of the American Statistical Association
Volume104
Issue number485
DOIs
StatePublished - Mar 1 2009
Externally publishedYes

Keywords

  • Empirical bayes
  • Genetic epidemiology
  • LASSO (Least Absolute Shrinkage and Selection Operator)
  • Model averaging
  • Model robustness
  • Model selection

ASJC Scopus subject areas

  • Statistics and Probability
  • Statistics, Probability and Uncertainty

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