Disease Gallery – Asthma

We analyzed the differences between Th2-mediated and non-Th2 asthma at a genetic level using data from 7,500 Th2-mediated and 15,000 non-Th2 asthmatics, as well as with 75,000 age and sex matched controls. precisionlife identified clear differences in the SNPs, genes and pathways associated with Th2 and non-Th2 disease.

The UK Biobank provides high-quality genotype assay results and deep phenotype information on approximately 550,000 middle-aged UK residents with diverse health and wellness backgrounds. This dataset is a massively enabling resource for the study of disease populations using the precisionlife platform.

Asthma is a broad diagnostic label given to a diverse set of conditions that exhibit similar clinical features – chronic airway inflammation, reversible airflow obstruction, wheezing, shortness of breath, chest tightness etc. While it is now generally acknowledged that several underlying pathophysiological processes can lead to asthma, most asthma patients continue to be treated using a one-size-fits-all approach.

This usually involves a combination of an inhaled corticosteroid (ICS), a long-acting β2 agonist (LABA), and a leukotriene inhibitor, as well as a short-acting bronchodilator – typically a short-acting β2 agonist – used as a rescue agent during acute episodes.

Treatment-refractory asthmatics form a relatively large group of patients suffering from frequent, severe asthma exacerbations, which are challenging to control. Four new biologic approaches are now the backbone of treatment for these patients. However all the approved asthma biologics target Th2-mediated (Th2-high) asthma, a subtype of the disease characterized by an underlying Th2 cell-mediated (Type 2) inflammatory response in the lungs’ airways. None of these treatments address the needs of Th2-low or non-Th2 asthma patients, leaving a high level of unmet need in severe, refractory asthma.

We therefore wanted to study the differences between Th2-mediated and non-Th2 asthma at a genetic level. To do this we went to UK Biobank to identify a cohort of asthma patients whose disease appeared to be Th2-mediated and another that appeared to be non-Th2 asthmatics. We used age and sex matched non-asthmatics as a control population. The datasets were constructed, run through precisionlife and the SNPs, genes and pathways associated with Th2 and non-Th2 disease identified and then compared. This was a fully automated process, taking less than 8 hours.

The differences between the two disease populations are immediately clear. There is significant difference between the pathways involved in the two diseases, showing the role of different targets and therefore the opportunity for new (or repurposed) treatments that will be more effective for the non-Th2 asthma group. We are investigating these and developing confirmation of effect on phenotype in disease assays & models.