Genome-wide association analysis in diverse inbred mice: power and population structure. Mus musculus

The discovery of quantitative trait loci (QTL) in model organisms has relied heavily on the ability to perform controlled breeding to generate genotypic and phenotypic diversity. Recently, we and others have demonstrated the use of a set of diverse inbred mice as a QTL mapping population. The use of this population has many advantages, including increased phenotypic diversity, a higher recombination frequency and the ability to collect genotype data in community databases. However, these methods are complicated by inherent population structure and the inability to accurately assess statistical power. To address these issues, we measured gene expression levels in hypothalamus across the diverse inbred mapping population. We then mapped these phenotypes as quantitative traits with our association algorithm, resulting in a large set of expression QTLs. We utilized these eQTLs (and specifically the cis-eQTLs) to devise a relative measure of statistical power which does not rely on parametrically simulated data. Finally, we utilized this approach to develop and optimize a novel method of accounting for population structure in the Mouse Diversity Panel. Keywords: strain and gender Overall design: samples were taken from naïve mice of different strains and both genders