Largest genetic study of asthma points towards better treatments

One in seven children in the UK suffers from asthma, which is caused by inflammation and narrowing of the airways in the lungs and results in difficulty breathing.

The causes of the disease are poorly understood, but genetic and environmental factors are thought to play roughly equal roles.

The new study, which was co-ordinated by researchers from Imperial College London, was performed by the GABRIEL consortium, a collaboration of 164 scientists from 19 countries in Europe, along with other groups in the UK, Canada and Australia. The findings are published this week in the 'New England Journal of Medicine'.

The researchers looked at DNA samples from 10 000 children and adults with asthma, and 16 000 non-asthmatics to pinpoint differences in genetic code.

The seven locations identified did not have strong enough effects to be useful for predicting asthma early in life, but the findings point the way toward better targeted therapy.

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 can trigger the condition. However, the study found that genes controlling the levels of antibodies causing 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 in the lining of the airways. This does not mean that allergies are not important, but it does mean that concentrating therapies only on allergies will not effectively treat the whole disease."

Some of the genes identified are involved in signalling pathways that tell the immune system when the lining of the airways has been damaged. Other genes appear to control how quickly the airways heal after they have been injured. Identifying these genes should help direct research into new treatments for asthma, the researchers suggest.

"Asthma is a complex disease in which many different parts of the immune system can become activated,” said Professor 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."

Professor David Strachan, Professor of Epidemiology at St George's, University of London, who also co-authored the study, said: "Asthma has often been considered a single disease, but our genetic findings suggest that childhood-onset asthma may differ biologically from asthma that is acquired in adult life. The GABRIEL consortium is now investigating whether the causes of asthma differ between people with and without these newly discovered genetic variants."

The findings reveal that genetic testing would not help predict who is likely to develop the disease, confirming 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 charity Asthma UK and the Wellcome Trust.