@article{372ea46c796d437f9c035a72375f2291,
title = "The integration of epistasis network and functional interactions in a GWAS implicates RXR pathway genes in the immune response to smallpox vaccine",
abstract = "Although many diseases and traits show large heritability, few genetic variants have been found to strongly separate phenotype groups by genotype. Complex regulatory networks of variants and expression of multiple genes lead to small individual-variant effects and difficulty replicating the effect of any single variant in an affected pathway. Interaction network modeling of GWAS identifies effects ignored by univariate models, but population differences may still cause specific genes to not replicate. Integrative network models may help detect indirect effects of variants in the underlying biological pathway. In this study, we used gene-level functional interaction information from the Integrative Multi-species Prediction (IMP) tool to reveal important genes associated with a complex phenotype through evidence from epistasis networks and pathway enrichment. We test this method for augmenting variant-based network analyses with functional interactions by applying it to a smallpox vaccine immune response GWAS. The integrative analysis spotlights the role of genes related to retinoid X receptor alpha (RXRA), which has been implicated in a previous epistasis network analysis of smallpox vaccine.",
author = "McKinney, {Brett A.} and Caleb Lareau and Oberg, {Ann L.} and Kennedy, {Richard B.} and Ovsyannikova, {Inna G.} and Poland, {Gregory A.}",
note = "Funding Information: Dr. Poland is the chair of a Safety Evaluation Committee for novel investigational vaccine trials being conducted by Merck Research Laboratories. Dr. Poland offers consultative advice on vaccine development to Merck & Co. Inc., CSL Biotherapies, Avianax, Dynavax, Novartis Vaccines and Therapeutics, Emergent Biosolutions, Adjuvance, Microdermis, Seqirus, NewLink, Protein Sciences, GSK Vaccines, and Sanofi Pasteur. Drs. Inna Ovsyannikova and Gregory Poland hold two patents related to vaccinia and measles peptide research: U.S. Patent “Vaccinia Virus Polypeptides,” U.S. Patent Number: 13/222,862 issued 31 August 2011; and U.S. Patent “Peptide Originating from Vaccinia Virus,” U.S. Patent Number: 7,622,120 issued 24 November 2009. Dr. Kennedy has received funding from Merck Research Laboratories to study waning immunity to mumps vaccine. These activities have been reviewed by the Mayo Clinic Conflict of Interest Review Board and are conducted in compliance with Mayo Clinic Conflict of Interest policies. This research has been reviewed by the Mayo Clinic Conflict of Interest Review Board and was conducted in compliance with Mayo Clinic Conflict of Interest policies. This does not alter the authors{\textquoteright} adherence to PLOS ONE policies on sharing data and materials. Funding Information: This project was funded by federal funds from the National Institute of Allergies and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under Contract No. HHSN266200400025C (N01AI40065). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2016 McKinney et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.",
year = "2016",
month = aug,
doi = "10.1371/journal.pone.0158016",
language = "English (US)",
volume = "11",
journal = "PloS one",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "8",
}