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

Research output: Contribution to journalArticleResearchpeer review

Authors

  • Ludwig A. Hothorn
  • Ondrej Libiger
  • Daniel Gerhard

Research Organisations

External Research Organisations

  • The Scripps Research Translational Institute
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Details

Original languageEnglish
Article number59
JournalBMC genetics
Volume13
Publication statusPublished - 18 Jul 2012

Abstract

Background: 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).Results: 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.Conclusions: 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.

Keywords

    Genetic association study, Interaction, Quantitative traits, Variance heterogeneity

ASJC Scopus subject areas

Cite this

Model-specific tests on variance heterogeneity for detection of potentially interacting genetic loci. / Hothorn, Ludwig A.; Libiger, Ondrej; Gerhard, Daniel.
In: BMC genetics, Vol. 13, 59, 18.07.2012.

Research output: Contribution to journalArticleResearchpeer review

Hothorn LA, Libiger O, Gerhard D. Model-specific tests on variance heterogeneity for detection of potentially interacting genetic loci. BMC genetics. 2012 Jul 18;13:59. doi: 10.1186/1471-2156-13-59, https://doi.org/10.15488/623
Hothorn, Ludwig A. ; Libiger, Ondrej ; Gerhard, Daniel. / Model-specific tests on variance heterogeneity for detection of potentially interacting genetic loci. In: BMC genetics. 2012 ; Vol. 13.
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abstract = "Background: 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).Results: 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.Conclusions: 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.",
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AU - Gerhard, Daniel

N1 - Funding Information: We appreciate the two anonymous reviewers for their insightful and constructive comment. The work for the first author was partly supported by the German Science Foundation grand DfG-HO1687.

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N2 - Background: 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).Results: 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.Conclusions: 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.

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