Nonparametric modeling of longitudinal covariance structure in functional mapping of quantitative trait loci

John Stephen Yap, Jianqing Fan, Rongling Wu

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Estimation of the covariance structure of longitudinal processes is a fundamental prerequisite for the practical deployment of functional mapping designed to study the genetic regulation and network of quantitative variation in dynamic complex traits. We present a nonparametric approach for estimating the covariance structure of a quantitative trait measured repeatedly at a series of time points. Specifically, we adopt Huang et al.'s (2006, Biometrika 93, 85-98) approach of invoking the modified Cholesky decomposition and converting the problem into modeling a sequence of regressions of responses. A regularized covariance estimator is obtained using a normal penalized likelihood with an L2 penalty. This approach, embedded within a mixture likelihood framework, leads to enhanced accuracy, precision, and flexibility of functional mapping while preserving its biological relevance. Simulation studies are performed to reveal the statistical properties and advantages of the proposed method. A real example from a mouse genome project is analyzed to illustrate the utilization of the methodology. The new method will provide a useful tool for genome-wide scanning for the existence and distribution of quantitative trait loci underlying a dynamic trait important to agriculture, biology, and health sciences.

Original languageEnglish (US)
Pages (from-to)1068-1077
Number of pages10
JournalBiometrics
Volume65
Issue number4
DOIs
StatePublished - Dec 2009

All Science Journal Classification (ASJC) codes

  • Statistics and Probability
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

Keywords

  • Covariance estimation
  • Functional mapping
  • Longitudinal data
  • Multivariate normal mixture
  • Quantitative trait loci

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