Incorporating biological knowledge in the search for gene × gene interaction in genome-wide association studies

BMC Proceedings

Table 2 Number of tests with p-values < 10^-6, 10^-7, 10^-8

						No. p-Values below threshold^a (permutation p-value)
SNP set	Source	RA gene included in set	No. genes in set	Test^b	Ntests	<10^-6	<10^-7	<10^-8
Small cell lung cancer	KEGG	TRAF1	87	Main effects	3,429	6 (<0.001)	6 (<0.001)	3 (<0.001)
				Interaction	5,800,955	8 (0.081)	0 (1)	0 (1)
JAK-STAT signaling pathway	KEGG	STAT4	153	Main effects	3,253	0 (1)	0 (1)	0 (1)
				Interaction	5,169,188	7 (0.137)	3 (0.029)	0 (1)
Protein complex assembly	GO	TRAF1	214	Main effects	3,883	6 (<0.001)	6 (<0.001)	3 (<0.001)
				Interaction	7,277,905	292 (0.642)	193 (0.152)	151 (0.012)
Protein amino acid dephosphorylation	GO	PTPN22	73	Main effects	2,277	0 (1)	0 (1)	0 (1)
				Interaction	2,496,978	1 (0.735)	0 (1)	0 (1)
JAK-STAT cascade	GO	STAT4	41	Main effects	761	0 (1)	0 (1)	0 (1)
				Interaction	289,031	0 (1)	0 (1)	0 (1)
Activation of MAPK activity	GO	C5	47	Main effects	785	3 (<0.001)	3 (<0.001)	1 (<0.001)
				Interaction	307,355	0 (1)	0 (1)	0 (1)
Chemotaxis	GO	C5	112	Main effects	1,470	3 (<0.001)	3 (<0.001)	1 (<0.001)
				Interaction	1,065,328	1 (0.467)	0 (1)	0 (1)
Inflammatory response	GO	C5	180	Main effects	2,535	3 (<0.001)	3 (<0.001)	1 (<0.001)
				Interaction	3,163,945	8 (0.025)	0 (1)	0 (1)

^aEmpirical significance was determined by comparing the number of p-values below each threshold to a null distribution of the number obtained by permuting the phenotypes and performing main effects and interaction tests with the permuted data set.
^bInteraction tests are unadjusted.

ISSN: 1753-6561