Comorbidity of asthma and hypertension may be mediated by shared genetic dysregulation and drug side effects

Abstract

Asthma and hypertension are complex diseases coinciding more frequently than expected by chance. Unraveling the mechanisms of comorbidity of asthma and hypertension is necessary for choosing the most appropriate treatment plan for patients with this comorbidity. Since both diseases have a strong genetic component in this article we aimed to find and study genes simultaneously associated with asthma and hypertension. We identified 330 shared genes and found that they form six modules on the interaction network. A strong overlap between genes associated with asthma and hypertension was found on the level of eQTL regulated genes and between targets of drugs relevant for asthma and hypertension. This suggests that the phenomenon of comorbidity of asthma and hypertension may be explained by altered genetic regulation or result from drug side effects. In this work we also demonstrate that not only drug indications but also contraindications provide an important source of molecular evidence helpful to uncover disease mechanisms. These findings give a clue to the possible mechanisms of comorbidity and highlight the direction for future research.

Figure 1

Identification and characterization of gene modules associated with asthma and hypertension. Network nodes represent genes and are colored according to membership in a module. Nodes not assigned to clusters are shown in grey. Size of each node is proportional to the number of evidence sources supporting the association of corresponding gene with asthma or hypertension. All gene set overlap analysis results are shown in Supplementary Tables S2A–C.

Figure 2

Evidence sources supporting gene associations with asthma and hypertension. In this figure, we used node style similar to Fig. 1B in. Here, nodes represent genes associated with both asthma and hypertension, edges correspond gene interactions (only 257 nodes connected with at least one other node are shown). Genes are colored according to evidence sources (see figure legend) from which associations came from. The size of each node is proportional to the number of evidence sources supporting its association with asthma and hypertension. All 330 genes associated with asthma and hypertension annotated with evidence types supporting associations are listed in Supplementary Table S1.

Figure 3

Relationships between genes and drugs indicated and contraindicated in asthma and hypertension. All target genes significantly overrepresented in one of four drug groups are shown. Drugs influencing both diseases and target genes overrepresented in more than one group are shown with bold frames.