Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Oct;17(10):1231-40.
doi: 10.1038/ejhg.2009.15. Epub 2009 Mar 11.

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

Mathieu Emily  1 , Thomas Mailund, Jotun Hein, Leif Schauser, Mikkel Heide Schierup
Affiliations

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

Mathieu Emily et al. Eur J Hum Genet. 2009 Oct.

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Overall analysis of the WTCCC data. Quantile–quantile plots of the test statistic observed in the seven studied diseases. The shaded region is the 95% concentration band, calculated assuming independent SNP pairs.
Figure 2
Figure 2
QQ plot for Crohn's disease (CD). Quantile–quantile plots of the test statistic observed for the CD. The black dots correspond to the entire data set. The blue dots result from the removal of SNP pairs included in APC-IQGAP1 regions. The shaded region shows the 95% concentration band for the non-interaction hypothesis.
See this image and copyright information in PMC

Comment in

References

    1. Consortium International Human Genome Sequencing Initial sequencing and analysis of the human genome. Nature. 2001;409:860–921. - PubMed
    1. HapMap The International HapMap Project. Nature. 2003;426:789–796. - PubMed
    1. The Wellcome Trust Case Control Consortium Genome-wide association study of 14 000 cases of seven common diseases and 3000 shared controls. Nature. 2007;447:661–678. - PMC - PubMed
    1. Curtis D. Allelic association studies of genome wide association data can reveal errors in marker position assignments. BMC Genetics. 2007;8:30. - PMC - PubMed
    1. Marchini J, Donnelly P, Cardon LR. Genome-wide strategies for detecting multiple loci that influence complex diseases. Nat Genet. 2005;37:413–417. - PubMed

Publication types