These results demonstrate that community detection is a good approach to visualizing the global and local structures of disease interaction. To further test whether the disease nodes and the connections between them are relevant to molecular mechanisms of disease, we incorporated chromatin-state annotations from the Roadmap Epigenomics Consortium and used them to extract biologically relevant subnetworks by using a similar approach. We only considered SNPs within enhancer regions for specific tissues for the current analysis. Seven tissue-specific DDNs were constructed from the shared variants in enhancer regions. The largest observed subnetwork where SNPs were in active enhancer regions was in the liver. The associated diseases for this tissue included 19 diseases, such as cirrhosis of the liver, chronic non-alcoholic liver disease, hyperlipidemia, morbid obesity, essential hypertension, and cardiovascular diseases, among others (Table S2). For adipose tissue, there were eight diseases in the subnetwork, including links between cardiovascular, nutritional, endocrine, and autoimmune diseases (Figure 4). Only two of the nodes in this subnetwork were connected to each other. Within the adipose subnetwork, we observed connections between cardiovascular diseases such as peripheral vascular disease, myocardial infarction, coronary artery disease, and abdominal aneurysm. Supporting these connections, previous studies have reported known links between increased gene expression in adipose tissue and cardiovascular diseases.24, 25 The second node was for type 1 diabetes, which had connections to psoriasis and Raynaud syndrome. Psoriasis and type 1 diabetes are both autoimmune diseases, and they share associations with the variation in the human leukocyte antigen (HLA) region. Numerous studies have identified strong connections between the pathogenesis of these autoimmune diseases and variations in HLA.38, 39
Figure 4 Diseases with Shared Enhancers in Adipose Tissue
The highlighting of disease nodes in the network indicates that the shared SNPs between these diseases are located in the enhancer region of the nearby gene.