Incorporating Biological Knowledge in the Search for Gene × Gene Interaction in Genome-Wide Association Studies
Date
2009-12-15
DOI
Authors
Manning, Alisa K.
Ngwa, Julius Suh
Hendricks, Audrey E.
Liu, Ching-Ti
Johnson, Andrew D.
Dupuis, Josée
Cupples, L. Adrienne
Version
OA Version
Citation
Manning, Alisa K, Julius Suh Ngwa, Audrey E Hendricks, Ching-Ti Liu, Andrew D Johnson, Josée Dupuis, L Adrienne Cupples. "Incorporating biological knowledge in the search for gene × gene interaction in genome-wide association studies" BMC Proceedings 3(Suppl 7):S81. (2009)
Abstract
We sought to find significant gene × gene interaction in a genome-wide association analysis of rheumatoid arthritis (RA) by performing pair-wise tests of interaction among collections of single-nucleotide polymorphisms (SNPs) obtained by one of two methods. The first method involved screening the results of the genome-wide association analysis for main effects p-values < 1 × 10-4. The second method used biological databases such as the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes to define gene collections that each contained one of four genes with known associations with RA: PTPN22, STAT4, TRAF1, and C5. We used a permutation approach to determine whether any of these SNP sets had empirical enrichment of significant interaction effects. We found that the SNP set obtained by the first method was significantly enriched with significant interaction effects (empirical p = 0.003). Additionally, we found that the "protein complex assembly" collection of genes from the Gene Ontology collection containing the TRAF1 gene was significantly enriched with interaction effects with p-values < 1 × 10-8 (empirical p = 0.012).
Description
License
Copyright 2009 Manning et al; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.