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Originally published as Genetics Published Articles Ahead of Print on May 27, 2009.
Genetics, Vol. 182, 1263-1277, August 2009, Copyright © 2009
doi:10.1534/genetics.109.100727
Mapping in Structured Populations by Resample Model Averaging
William Valdar*,1,
Christopher C. Holmes
,
,
Richard Mott* and
Jonathan Flint*
* Wellcome Trust Centre for Human Genetics, Oxford OX3 7BN, United Kingdom, Department of Statistics, University of Oxford, Oxford, OX1 3TG, United Kingdom and MRC Mammalian Genetics Unit, MRC Harwell, Harwell OX11 0RD, United Kingdom
1 Corresponding author: Wellcome Trust Centre for Human Genetics, Roosevelt Dr., Oxford OX3 7BN, United Kingdom.
E-mail: valdar{at}well.ox.ac.uk
Highly recombinant populations derived from inbred lines, such as advanced intercross lines and heterogeneous stocks, can be used to map loci far more accurately than is possible with standard intercrosses. However, the varying degrees of relatedness that exist between individuals complicate analysis, potentially leading to many false positive signals. We describe a method to deal with these problems that does not require pedigree information and accounts for model uncertainty through model averaging. In our method, we select multiple quantitative trait loci (QTL) models using forward selection applied to resampled data sets obtained by nonparametric bootstrapping and subsampling. We provide model-averaged statistics about the probability of loci or of multilocus regions being included in model selection, and this leads to more accurate identification of QTL than by single-locus mapping. The generality of our approach means it can potentially be applied to any population of unknown structure.
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