Author
Listed:
- Christine Herold
- Alfredo Ramirez
- Dmitriy Drichel
- André Lacour
- Tatsiana Vaitsiakhovich
- Markus M Nöthen
- Frank Jessen
- Wolfgang Maier
- Tim Becker
Abstract
Deviation from multiplicativity of genetic risk factors is biologically plausible and might explain why Genome-wide association studies (GWAS) so far could unravel only a portion of disease heritability. Still, evidence for SNP-SNP epistasis has rarely been reported, suggesting that 2-SNP models are overly simplistic. In this context, it was recently proposed that the genetic architecture of complex diseases could follow limiting pathway models. These models are defined by a critical risk allele load and imply multiple high-dimensional interactions. Here, we present a computationally efficient one-degree-of-freedom “supra-multiplicativity-test” (SMT) for SNP sets of size 2 to 500 that is designed to detect risk alleles whose joint effect is fortified when they occur together in the same individual. Via a simulation study we show that the SMT is powerful in the presence of threshold models, even when only about 30–45% of the model SNPs are available. In addition, we demonstrate that the SMT outperforms standard interaction analysis under recessive models involving just a few SNPs. We apply our test to 10 consensus Alzheimer’s disease (AD) susceptibility SNPs that were previously identified by GWAS and obtain evidence for supra-multiplicativity () that is not attributable to either two-way or three-way interaction.
Suggested Citation
Christine Herold & Alfredo Ramirez & Dmitriy Drichel & André Lacour & Tatsiana Vaitsiakhovich & Markus M Nöthen & Frank Jessen & Wolfgang Maier & Tim Becker, 2013.
"A One-Degree-of-Freedom Test for Supra-Multiplicativity of SNP Effects,"
PLOS ONE, Public Library of Science, vol. 8(10), pages 1-10, October.
Handle:
RePEc:plo:pone00:0078038
DOI: 10.1371/journal.pone.0078038
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0078038. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.