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PMID: 19277065 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

European journal of human genetics : EJHG ·Vol. 17 ·No. 10 ·2009-10-00 ·Pages 1231-40

Emily M, Mailund T, Hein J, Schauser L, Schierup MH

Abstract

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.

MeSH Terms
Alleles Arthritis, Rheumatoid/genetics Bipolar Disorder/genetics Computational Biology/methods Crohn Disease/genetics Epistasis, Genetic Genome-Wide Association Study Genotype Humans Hypertension/genetics Models, Genetic Models, Statistical Phenotype Protein Interaction Mapping Risk Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Emily Mathieu
Bioinformatics Research Center, University of Aarhus, C. F. Møllers Alle, Aarhus C, Denmark. mathieu.emily@uhb.fr
Mailund Thomas
Hein Jotun
Schauser Leif
Schierup Mikkel Heide
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Article Info
Journal
European journal of human genetics : EJHG
Abbr.
Eur J Hum Genet
ISSN
1476-5438
DOI
10.1038/ejhg.2009.15
Email
mathieu.emily@uhb.fr
Published
2009-10-00
Epub
2009-00-11
Pages
1231-40
Language
English
Region
England
NLM ID
9302235
PMCID
PMC2986645
Subset
IM
Corrections
CommentIn
PMID: 19277066
External Links
PubMed source DOI: 10.1038/ejhg.2009.15 PMC Full Text View journal details
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