Imperial: Largest-ever study of asthma genetics throws up new targets for therapy

Research lead

An international study of DNA from over 26,000 people has identified several genetic variants that substantially increase an individual’s susceptibility to asthma, which could form the bases on new approaches to treating the disorder.

The study, co-ordinated by researchers from Imperial College London, was performed by GABRIEL a consortium involving 164 scientists in 19 countries in Europe, along with groups in Canada and Australia. It analysed DNA samples from 10,000 children and adults with asthma and 16,000 non-asthmatics.

“Asthma is a complex disease in which many different parts of the immune system can become activated,” said William Cookson, Director of Respiratory Sciences at Imperial College London, who co-ordinated the study. “One of the problems with asthma research has been choosing where to intervene in the disease pathways. Our study now highlights targets for effective asthma therapies, and suggests that therapies against these targets will be of use to large numbers of asthmatics in the population.”

The whole genome scan pinpointed seven locations on the genome associated with asthma. While the causes of the disease are poorly understood, genetic and environmental factors are thought to play roughly equal roles.

The new genetic variants discovered by the study were found in more than a third of the children with asthma. The gene with the strongest effect on children did not affect adults, and adult-onset asthma was more weakly linked to other genetic differences, suggesting that it may differ biologically from childhood-onset asthma.

Childhood asthma, which affects boys more than girls and can persist throughout life, is often linked to allergies, and it has been assumed that these allergies can trigger the condition. However, the study found that genes controlling the levels of antibodies that cause allergies had little effect on the presence of asthma, suggesting that allergies are more likely to be a consequence of asthma than a cause.

Miriam Moffatt, Professor of Human Genetics at Imperial College London and one of the study’s leaders, said, “As a result of genetic studies we now know that allergies may develop as a result of defects of the lining of the airways in asthma. This does not mean that allergies are not important, but it does mean that concentrating therapies only on allergy will not effectively treat the whole disease.”

Some of the genes identified are involved in signalling pathways that alert the immune system when the lining of the airways has been damaged. Other genes control how quickly the airways heal after injury.

The study also found that the genes associated with asthma did not have strong enough effects to be useful for predicting early in life which children might eventually develop the disease. This indicates that environmental factors are also very important in causing asthma to develop. The GABRIEL consortium is working to identify environmental exposures that could protect against the illness.

The study was primarily funded by the European Commission, the French Ministry for Higher Education and Research, the charities Asthma UK and the Wellcome Trust.