Manning Alisa K, Ngwa Julius Suh, Hendricks Audrey E, Liu Ching-Ti, Johnson Andrew D, Dupuis Josée, Cupples L Adrienne
School of Public Health, Boston University, 715 Albany Street, Boston, Massachusetts 02118, USA.
BMC Proc. 2009 Dec 15;3 Suppl 7(Suppl 7):S81. doi: 10.1186/1753-6561-3-s7-s81.
We sought to find significant gene x 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 x 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 x 10-8 (empirical p = 0.012).
我们试图通过对两种方法之一获得的单核苷酸多态性（SNP）集合进行成对相互作用测试，在类风湿性关节炎（RA）的全基因组关联分析中找到显著的基因×基因相互作用。第一种方法是筛选全基因组关联分析结果中主效应p值<1×10⁻⁴的情况。第二种方法使用诸如基因本体论和京都基因与基因组百科全书等生物数据库来定义基因集合，每个集合包含与RA已知关联的四个基因之一：PTPN22、STAT4、TRAF1和C5。我们使用排列法来确定这些SNP集合中是否有任何集合具有显著相互作用效应的经验性富集。我们发现通过第一种方法获得的SNP集合显著富集了显著的相互作用效应（经验p = 0.003）。此外，我们发现来自包含TRAF1基因的基因本体论集合中的“蛋白质复合体组装”基因集合，其相互作用效应显著富集，p值<1×10⁻⁸（经验p = 0.012）。
