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G3 (Bethesda). 2018 Dec 10;8(12):3783-3790. doi: 10.1534/g3.118.200194.

Mean-Variance QTL Mapping Identifies Novel QTL for Circadian Activity and Exploratory Behavior in Mice.

Author information

1
Department of Genetics.
2
Bioinformatics and Computational Biology Curriculum.
3
The Jackson Laboratory.
4
Howard Hughes Medical Institute, Department of Neuroscience, University of Texas Southwestern Medical Center, Dallas, TX 75390.
5
Department of Genetics william.valdar@unc.edu.
6
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.

Abstract

We illustrate, through two case studies, that "mean-variance QTL mapping"-QTL mapping that models effects on the mean and the variance simultaneously-can discover QTL that traditional interval mapping cannot. Mean-variance QTL mapping is based on the double generalized linear model, which extends the standard linear model used in interval mapping by incorporating not only a set of genetic and covariate effects for mean but also set of such effects for the residual variance. Its potential for use in QTL mapping has been described previously, but it remains underutilized, with certain key advantages undemonstrated until now. In the first case study, a reduced complexity intercross of C57BL/6J and C57BL/6N mice examining circadian behavior, our reanalysis detected a mean-controlling QTL for circadian wheel running activity that interval mapping did not; mean-variance QTL mapping was more powerful than interval mapping at the QTL because it accounted for the fact that mice homozygous for the C57BL/6N allele had less residual variance than other mice. In the second case study, an intercross between C57BL/6J and C58/J mice examining anxiety-like behaviors, our reanalysis detected a variance-controlling QTL for rearing behavior; interval mapping did not identify this QTL because it does not target variance QTL. We believe that the results of these reanalyses, which in other respects largely replicated the original findings, support the use of mean-variance QTL mapping as standard practice.

KEYWORDS:

DGLM; mQTL; mvQTL; vQTL; variance heterogeneirty

PMID:
30389793
PMCID:
PMC6288835
DOI:
10.1534/g3.118.200194
[Indexed for MEDLINE]
Free PMC Article

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