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Open Access Research article

Model-specific tests on variance heterogeneity for detection of potentially interacting genetic loci

Ludwig A Hothorn12*, Ondrej Libiger2 and Daniel Gerhard1

Author Affiliations

1 Institute of Biostatistics, Leibniz University Hannover, D–30419 Hannover, Germany

2 Scripps Genomic Medicine, The Scripps Research Institute, La Jolla, CA–92037, USA

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BMC Genetics 2012, 13:59  doi:10.1186/1471-2156-13-59

Published: 18 July 2012



Trait variances among genotype groups at a locus are expected to differ in the presence of an interaction between this locus and another locus or environment. A simple maximum test on variance heterogeneity can thus be used to identify potentially interacting single nucleotide polymorphisms (SNPs).


We propose a multiple contrast test for variance heterogeneity that compares the mean of Levene residuals for each genotype group with their average as an alternative to a global Levene test. We applied this test to a Bogalusa Heart Study dataset to screen for potentially interacting SNPs across the whole genome that influence a number of quantitative traits. A user-friendly implementation of this method is available in the R statistical software package multcomp.


We show that the proposed multiple contrast test of model-specific variance heterogeneity can be used to test for potential interactions between SNPs and unknown alleles, loci or covariates and provide valuable additional information compared with traditional tests. Although the test is statistically valid for severely unbalanced designs, care is needed in interpreting the results at loci with low allele frequencies.

Genetic association study; Quantitative traits; Interaction; Variance heterogeneity