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Biostatistics Advance Access published online on April 14, 2005
Biostatistics, doi:10.1093/biostatistics/kxi019
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© The Author 2005. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oupjournals.org.
Received March 8, 2004
Revised December 20, 2004
Accepted January 19, 2005

Article

A General Model for Detecting Genetic Determinants Underlying Longitudinal Traits with Unequally Spaced Measurements and Nonstationary Covariance Structure

Wei Hou 1, Cynthia W. Garvan 1, Wei Zhao 1, Marylou Behnke 2, Fonda Davis Eyler 2, and Rongling Wu 1*

1 Department of Statistics, University of Florida, Gainesville, FL 32611 USA
2 Department of Pediatrics, University of Florida, Gainesville, FL 32611 USA

* To whom correspondence should be addressed.
Rongling Wu, E-mail: rwu{at}stat.ufl.edu


  Abstract

A mixture model for determining quantitative trait loci (QTL) affecting growth trajectories has been proposed in the literature. In this article, we extend this model to a more general situation in which longitudinal traits for each subject are measured at unequally spaced time intervals, different subjects have different measurement patterns, and the residual correlation within subjects is nonstationary. We derive an EM-simplex hybrid algorithm to estimate the allele frequencies, Hardy-Weinberg disequilibrium and linkage disequilibrium between QTL in the original population and parameters contained in the growth equation and in the covariance structure. A worked example of head circumference growth in 145 children is used to validate our extended model. A simulation study is performed to examine the statistical properties of the parameter estimation obtained from this example. Finally, we discuss the implications and extensions of our model for detecting QTL that affect growth trajectories.


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[Abstract] [Full Text] [PDF]


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