Description: We present vqtl, an R package for mean-variance QTL mapping. This QTL mapping approach tests for genetic loci that influence the mean of the phenotype, termed mean QTL, the variance of the phenotype, termed variance QTL, or some combination of the two, termed mean-variance QTL. It is unique in its ability to correct for variance heterogeneity arising not only from the QTL itself but also from nuisance factors, such as sex, batch, or housing. This package provides functions to conduct genome scans, run permutations to assess the statistical significance, and make informative plots to communicate results. Because it is inter-operable with the popular qtl package and uses many of the same data structures and input patterns, it will be straightforward for geneticists to analyze future experiments with vqtl as well as re-analyze past experiments, possibly discovering new QTL.

Description: Standard QTL mapping procedures seek to identify genetic loci affecting the phenotypic mean while assuming that all individuals have the same residual variance. But when the residual variance differs systematically between groups, perhaps due to a genetic or environmental factor, such standard procedures can falter: in testing for QTL associations, they attribute too much weight to observations that are noisy and too little to those that are precise, resulting in reduced power and and increased susceptibility to false positives. The negative effects of such "background variance heterogeneity" (BVH) on standard QTL mapping have received little attention until now, although the subject is closely related to work on the detection of variance-controlling genes. Here we use simulation to examine how BVH affects power and false positive rate for detecting QTL affecting the mean (mQTL), the variance (vQTL), or both (mvQTL). We compare linear regression for mQTL and Levene’s test for vQTL, with tests more recently developed, including tests based on the double generalized linear model (DGLM), which can model BVH explicitly. We show that, when used in conjunction with a suitable permutation procedure, the DGLM-based tests accurately control false positive rate and are more powerful than the other tests. We also find that some adverse effects of BVH can be mitigated by applying a rank inverse normal transform. We apply our novel approach, which we term "mean-variance QTL mapping", to publicly available data on a mouse backcross and, after accommodating BVH driven by sire, detect a new mQTL for bodyweight.