A Model Selection Approach for the Identification of Quantitative Trait Loci in Experimental Crosses, Allowing Epistasis

Author:

Manichaikul Ani1,Moon Jee Young2,Sen Śaunak3,Yandell Brian S24,Broman Karl W5

Affiliation:

1. Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22908

2. Department of Statistics

3. Department of Epidemiology and Biostatistics, University of California, San Francisco, California 94143

4. Department of Horticulture and

5. Department of Biostatistics and Medical Informatics, University of Wisconsin, Madison, Wisconsin 53706 and

Abstract

Abstract 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.

Publisher

Oxford University Press (OUP)

Subject

Genetics

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