Genetic Variants Linked to Asthma, Mucus Production

UK investigators conducted the first large study seeking to understand whether the same or different genes explain why some people experience more severe asthma symptoms.

Ian Sayers, PhD

A new study has revealed several genetic variants linked to moderate and severe asthma and mucus production, bringing physicians a step closer better disease management.

For some patients, despite taking medications at high doses, their asthma symptoms remain difficult to control. According to the American Academy of Allergy, Asthma and Immunology (AAAAI), the prevalence of severe asthma is 3.6% among adults. In these cases, quality of life is heavily impacted, causing missed days at work and increased hospitalizations; some studies suggest that severe asthma raises the risk for other lung conditions, such as chronic obstructive pulmonary disease (COPD) and emphysema.

According to researchers, this study is the largest to evaluate the genetic links to moderate-to-severe asthma, investigating 10,549 cases with 47,146 healthy controls to help identify genetic differences that might explain asthma that remains severe despite treatment.

“We know there are genes that make some people more likely to develop asthma, but there hadn’t yet been a large study that set out to understand whether the same genes or different genes explain why some people experience very severe symptoms and don’t respond well to treatment compared to others,” Ian Sayers, PhD, of the University of Nottingham and lead author of the study, told MD Magazine®.

The study pooled subjects from two UK cohorts: the Genetics of Asthma Severity and Phenotypes (GASP) Initiative and the Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes (U-BIOPRED) project. Data for patient-level controls and cases of European ancestry were taken from the UK Biobank.

Cases were defined as having moderate-to-severe asthma if they had a doctor diagnosis and were taking prescribed medication. Controls were defined as not having asthma, rhinitis, eczema, allergy, emphysema, or chronic bronchitis.

Out of the 24 genome-wide signals associated with moderate-to-severe asthma, 3 have been identified for the first time: rs10905284 A allele in GATA3, rs11603634 G allele in the MUC5AC area, and rs560026225 GATT allele near KIAA1109. Notably, the rs11603634 G allele was associated with heightened expression of MUC5AC, which is responsible for mucus production.

“Our study showed that most of the genes we identified are important in both mild-to-severe asthma, which is important because it suggests additional non-genetic factors may be important for the development of severe asthma, such as the environment,” said Dr. Louise Wain, British Lung Foundation Chair in Respiratory Research, University of Leicester. “It also suggests that new medicines targeting these genes may also be effective in more severe forms of asthma.”

Treatments for chronic illnesses like asthma have grown leaps and bounds, but we are still far off from more personalized medicine, where patients are given treatments tailor made for them. This study helps steer research in that direction.

“Most genetic studies of asthma to date, including ours, have used data from European populations,” said Nick Shrine, PhD, from the University of Leicester, who led the data analysis. “We now need bigger studies of more severe forms of asthma in other populations to confirm that the same genes are indeed important in those populations as well.”

The study, “Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study”, was published December 11 online in The Lancet Respiratory Medicine.