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Multiple Testing for SNP-SNP Interactions

Boulesteix Anne-Laure, Strobl Carolin, Weidinger Stefan, Wichmann H.-Erich and Wagenpfeil Stefan
Additional contact information
Boulesteix Anne-Laure: Sylvia Lawry Centre and Institute for Medical Statistics and Epidemiology, Technical University of Munich
Strobl Carolin: Department of Statistics, University of Munich
Weidinger Stefan: Department of Dermatology and Allergy Biederstein, Technical University of Munich
Wichmann H.-Erich: Department of Epidemiology, GSF
Wagenpfeil Stefan: Institute for Medical Statistics and Epidemiology, Technical University of Munich

Statistical Applications in Genetics and Molecular Biology, 2007, vol. 6, issue 1, 1-24

Abstract: Most genetic diseases are complex, i.e. associated to combinations of SNPs rather than individual SNPs. In the last few years, this topic has often been addressed in terms of SNP-SNP interaction patterns given as expressions linked by logical operators. Methods for multiple testing in high-dimensional settings can be applied when many SNPs are considered simultaneously. However, another less well-known multiple testing problem arises within a fixed subset of SNPs when the logic expression is chosen optimally. In this article, we propose a general asymptotic approach for deriving the distribution of the maximally selected chi-square statistic in various situations. We show how this result can be used for testing logic expressions - in particular SNP-SNP interaction patterns - while controlling for multiple comparisons. Simulations show that our method provides multiple testing adjustments when the logic expression is chosen such as to maximize the statistic. Its benefit is demonstrated through an application to a real dataset from a large population-based study considering allergy and asthma in KORA. An implementation of our method is available from the Comprehensive R Archive Network (CRAN) as R package 'SNPmaxsel'.

Date: 2007
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DOI: 10.2202/1544-6115.1315

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