A model selection approach for the identification of quantitative trait loci in experimental crosses, allowing epistasis.
The identification of quantitative trait loci (QTL) and their interactions is a crucial step toward the discovery of genes responsible for variation in experimental crosses. The problem is best viewed as one of model selection, and the most important aspect of the problem is the comparison of models of different sizes. We present a penalized likelihood approach, with penalties on QTL and pairwise interactions chosen to control false positive rates. This extends the work of Broman and Speed to allow for pairwise interactions among QTL. A conservative version of our penalized LOD score provides strict control over the rate of extraneous QTL and interactions; a more liberal criterion is more lenient on interactions but seeks to maintain control over the rate of inclusion of false loci. The key advance is that one needs only to specify a target false positive rate rather than a prior on the number of QTL and interactions. We illustrate the use of our model selection criteria as exploratory tools; simulation studies demonstrate reasonable power to detect QTL. Our liberal criterion is comparable in power to two Bayesian approaches.
Manichaikul
Ani
A
Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908, USA.
Moon
Jee Young
JY
Sen
Saunak
S
Yandell
Brian S
BS
Broman
Karl W
KW
D000383:Agriculture; D000818:Animals; D003198:Computer Simulation; D003433:Crosses, Genetic; D004843:Epistasis, Genetic; D019143:Evolution, Molecular; D051379:Mice; D008957:Models, Genetic; D040641:Quantitative Trait Loci; D015203:Reproducibility of Results