Table 1.

Pro-inflammatory pathways in which mutated genes were detected in two large whole-genome DNA sequencing studies

Canonical Pathways [43]	P value	Canonical Pathways[44]	P value
NF-κB signaling	0.01	ATM signaling	0.00006
Toll like receptor signaling	0.02	LPS-stimulated MAPK signaling	0.0007
CD28 signaling in T helper cells	0.04	CC receptor 3 signaling in eosinophils	0.0001
Leukocyte extravasation signaling	0.04	Chemokine signaling	0.001
CXCR4 signaling	0.05	T-cell receptor signaling	0.01
Chemokine signaling	0.06	Toll-like receptor signaling	0.02
B-cell receptor signaling	0.06	B-cell receptor signaling	0.02
ATM signaling	0.08	IL-12 signaling and production in macrophages	0.03
IL-4 signaling	0.09	IL-3 signaling	0.03
IL-12 signaling and production in macrophages	0.09	IL-1 signaling	0.04
IL-15 signaling	0.1	CXCR4 signaling	0.04
Role of NFAT in the regulation of the immune response	0.1	MIF regulation of innate immunity	0.05
		IL-8 signaling	0.05
		Acute phase response signaling	0.06
		NF-κB signaling	0.06
		IL-17 signaling	0.07
		PI3K signaling in B lymphocytes	0.1
		B-cell activating factor signaling	0.1
		Role of NFAT in the regulation of the immune response	0.1

NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells, ATM, ataxia telangiectasia-mutated; CD, cluster of differentiation; CXCR4, chemokine receptor type 4; IL, interleukin; NFAT, nuclear factor of activated T-cells; MIF, migration inhibitory factor; NK, natural killer; Fcγ, Fc gamma; PI3K, phosphatidylinositide 3-kinases; FcγRIIB, Fcγ receptor IIB; Wnt, Int and Wg gene; MAPK, mitogen-activated protein kinase; BAFF, B-cell activating factor;

The functional analysis presented in this table was generated through the use of IPA (Ingenuity Systems (www.ingenuity.com). Fisher’s exact test was used to calculate a P-value determining the probability that the association between the mutated genes and the canonical pathway could be explained by chance. Pro-inflammatory pathways in which mutated genes were detected in the study of Quesada et al. [43] are depicted in columns 1 and 2, and in the study of Wang et al. [44], in columns 3 and 4. Both studies detected mutations in genes crucial for an inflammatory response, including cytokine signaling pathways (eg: IL-6), innate immunity activation pathways (eg: TLR signaling), chemokine signaling (eg: CXCR4) and pro-inflammatory transcription factors (eg: NF-κB signaling).