A generalized estimating equations approach to quantitative trait locus detection of non-normal traitsPeter C. Thomson
Biometry Unit, Faculty of Agriculture, Food and Natural Resources and Centre for Advanced Technologies in Animal Genetics and Reproduction (ReproGen), The University of Sydney, PMB 3, Camden NSW 2570, Australia
(Received 12 February 2002; accepted 22 January 2003)
To date, most statistical developments in QTL detection methodology have been directed at continuous traits with an underlying normal distribution. This paper presents a method for QTL analysis of non-normal traits using a generalized linear mixed model approach. Development of this method has been motivated by a backcross experiment involving two inbred lines of mice that was conducted in order to locate a QTL for litter size. A Poisson regression form is used to model litter size, with allowances made for under- as well as over-dispersion, as suggested by the experimental data. In addition to fixed parity effects, random animal effects have also been included in the model. However, the method is not fully parametric as the model is specified only in terms of means, variances and covariances, and not as a full probability model. Consequently, a generalized estimating equations (GEE) approach is used to fit the model. For statistical inferences, permutation tests and bootstrap procedures are used. This method is illustrated with simulated as well as experimental mouse data. Overall, the method is found to be quite reliable, and with modification, can be used for QTL detection for a range of other non-normally distributed traits.
Key words: QTL / non-normal traits / generalized estimation equation / litter size / mice
Correspondence and reprints: Peter C. Thomson
© INRA, EDP Sciences 2003