Using biological networks to search for interacting loci in genome-wide association studies.

Genome-wide association studies have identified a large number of single-nucleotide polymorphisms (SNPs) that individually predispose to diseases. However, many genetic risk factors remain unaccounted for. Proteins coded by genes interact in the cell, and it is most likely that certain variants main...

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Huvudupphovsmän: Emily, M, Mailund, T, Hein, J, Schauser, L, Schierup, M
Materialtyp: Journal article
Språk:English
Publicerad: 2009
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author Emily, M
Mailund, T
Hein, J
Schauser, L
Schierup, M
author_facet Emily, M
Mailund, T
Hein, J
Schauser, L
Schierup, M
author_sort Emily, M
collection OXFORD
description Genome-wide association studies have identified a large number of single-nucleotide polymorphisms (SNPs) that individually predispose to diseases. However, many genetic risk factors remain unaccounted for. Proteins coded by genes interact in the cell, and it is most likely that certain variants mainly affect the phenotype in combination with other variants, termed epistasis. An exhaustive search for epistatic effects is computationally demanding, as several billions of SNP pairs exist for typical genotyping chips. In this study, the experimental knowledge on biological networks is used to narrow the search for two-locus epistasis. We provide evidence that this approach is computationally feasible and statistically powerful. By applying this method to the Wellcome Trust Case-Control Consortium data sets, we report four significant cases of epistasis between unlinked loci, in susceptibility to Crohn's disease, bipolar disorder, hypertension and rheumatoid arthritis.
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spelling oxford-uuid:7adf701e-6cb0-4118-8b2c-bb97b9032ce32022-03-26T20:46:54ZUsing biological networks to search for interacting loci in genome-wide association studies.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7adf701e-6cb0-4118-8b2c-bb97b9032ce3EnglishSymplectic Elements at Oxford2009Emily, MMailund, THein, JSchauser, LSchierup, MGenome-wide association studies have identified a large number of single-nucleotide polymorphisms (SNPs) that individually predispose to diseases. However, many genetic risk factors remain unaccounted for. Proteins coded by genes interact in the cell, and it is most likely that certain variants mainly affect the phenotype in combination with other variants, termed epistasis. An exhaustive search for epistatic effects is computationally demanding, as several billions of SNP pairs exist for typical genotyping chips. In this study, the experimental knowledge on biological networks is used to narrow the search for two-locus epistasis. We provide evidence that this approach is computationally feasible and statistically powerful. By applying this method to the Wellcome Trust Case-Control Consortium data sets, we report four significant cases of epistasis between unlinked loci, in susceptibility to Crohn's disease, bipolar disorder, hypertension and rheumatoid arthritis.
spellingShingle Emily, M
Mailund, T
Hein, J
Schauser, L
Schierup, M
Using biological networks to search for interacting loci in genome-wide association studies.
title Using biological networks to search for interacting loci in genome-wide association studies.
title_full Using biological networks to search for interacting loci in genome-wide association studies.
title_fullStr Using biological networks to search for interacting loci in genome-wide association studies.
title_full_unstemmed Using biological networks to search for interacting loci in genome-wide association studies.
title_short Using biological networks to search for interacting loci in genome-wide association studies.
title_sort using biological networks to search for interacting loci in genome wide association studies
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