By integrating asthma GWAS results with our eSNP and Bayesian network, we were able to identify a network of 34 genes that highlights the molecular underpinnings of asthma (Figure 5 and Table S3). This network of genes is annotated as inflammatory response by the online tool DAVID [41] with an enrichment score of 3.27 (P = 7×10−6). Of particular interest is one Key Driver node, SOCS3 (suppressor of cytokine signaling 3). SOCS3 belongs to the SOCS family of genes that are cytokine-inducible negative regulators of cytokine signaling and play an important role in TH2-mediated allergic responses through control of the balance between TH1 and TH2 cells. It is implicated in both asthma and atopic dermatitis, as well as in regulating serum IgE levels [42]. Moriwaki and colleagues found that down-regulation of Socs3 in ovalbumin sensitized mice caused attenuation of eosinophilia and airway hyperresponsiveness generated by ovalbumin challenge [43].
