Automated construction and testing of multi-locus gene-gene associations |
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Authors: | Abo Ryan Knight Stacey Thomas Alun Camp Nicola J |
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Institution: | Department of Biomedical Informatics, University of Utah School of Medicine, UT, USA. ryan.abo@hsc.utah.edu |
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Abstract: | It has been argued that the missing heritability in common diseases may be in part due to rare variants and gene-gene effects. Haplotype analyses provide more power for rare variants and joint analyses across genes can address multi-gene effects. Currently, methods are lacking to perform joint multi-locus association analyses across more than one gene/region. Here, we present a haplotype-mining gene-gene analysis method, which considers multi-locus data for two genes/regions simultaneously. This approach extends our single region haplotype-mining algorithm, hapConstructor, to two genes/regions. It allows construction of multi-locus SNP sets at both genes and tests joint gene-gene effects and interactions between single variants or haplotype combinations. A Monte Carlo framework is used to provide statistical significance assessment of the joint and interaction statistics, thus the method can also be used with related individuals. This tool provides a flexible data-mining approach to identifying gene-gene effects that otherwise is currently unavailable. AVAILABILITY: http://bioinformatics.med.utah.edu/Genie/hapConstructor.html. |
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