Surfing a genetic association interaction network to identify modulators of antibody response to smallpox vaccine
β Scribed by Davis, N A; Crowe, J E; Pajewski, N M; McKinney, B A
- Book ID
- 109854964
- Publisher
- Nature Publishing Group
- Year
- 2010
- Tongue
- English
- Weight
- 391 KB
- Volume
- 11
- Category
- Article
- ISSN
- 1466-4879
No coin nor oath required. For personal study only.
β¦ Synopsis
The variation in antibody response to vaccination likely involves small contributions of numerous genetic variants, such as single-nucleotide polymorphisms (SNPs), which interact in gene networks and pathways. To accumulate the bits of genetic information relevant to the phenotype that are distributed throughout the interaction network, we develop a network eigenvector centrality algorithm (SNPrank) that is sensitive to the weak main effects, geneβgene interactions and small higher-order interactions through hub effects. Analogous to Google PageRank, we interpret the algorithm as the simulation of a random SNP surfer (RSS) that accumulates bits of information in the network through a dynamic probabilistic Markov chain. The transition matrix for the RSS is based on a data-driven genetic association interaction network (GAIN), the nodes of which are SNPs weighted by the main-effect strength and edges weighted by the geneβgene interaction strength. We apply SNPrank to a GAIN analysis of a candidate-gene association study on human immune response to smallpox vaccine. SNPrank implicates a SNP in the retinoid X receptor Ξ± (RXRA) gene through a network interaction effect on antibody response. This vitamin A- and D-signaling mediator has been previously implicated in human immune responses, although it would be neglected in a standard analysis because its significance is unremarkable outside the context of its network centrality. This work suggests SNPrank to be a powerful method for identifying network effects in genetic association data and reveals a potential vitamin regulation network association with antibody response.
π SIMILAR VOLUMES