An EU-funded study has identified several genetic variants that substantially increase susceptibility to asthma and which scientists claim will help them develop better therapies for the illness. The GABRIEL ('A multidisciplinary study to identify the genetic and environmental causes of asthma in the European Community') project received just over EUR 11 million under the 'Life sciences, genomics and biotechnology for health' Thematic area of the Sixth Framework Programme (FP6). The findings of the study were published in the New England Journal of Medicine.
The research team, led by scientists from Imperial College London in the UK, analysed DNA (deoxyribonucleic acid) samples from 10 000 children and adults with asthma, and 16 000 non-asthmatics. They then performed more than 500 000 genetic tests on each subject, covering all the genes in the human genome. The study, with contributions made by 164 scientists from 19 European countries plus Australia and Canada, pinpointed seven locations on the genome where differences in the genetic code were associated with asthma.
While some 300 million people worldwide have asthma, with 30 million of these living in Europe, the causes of the disease are poorly understood with genetic and environmental factors thought to play roughly equal roles. This study suggests that allergies are probably a consequence of asthma, rather than a cause of the disease, and that genetic testing would not help predict who is likely to develop the disease.
For example, 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 that cause allergies had little effect on the presence of asthma.
The new variants linked to asthma were found in more than a third of 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, implying that it may differ biologically from childhood-onset asthma.
'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,' said Professor David Strachan from St Georges, University of London, a co-author of the study. The team 'is now investigating whether the causes of asthma differ between people with and without these newly discovered genetic variants'.
'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,' said Professor Miriam Moffatt, Professor of Human Genetics at Imperial College London. '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 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, according to the researchers.
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 develop the disease. This indicates that environmental factors likewise play an important role in causing asthma to develop.
Co-author Professor Erika von Mutius at the University of Munich explained that the team was investigating the environmental causes of asthma 'particularly by dissecting the strong protective effects of living on a farm. In the next year we will be combining the results from the genetic and environmental wings of the GABRIEL study, and we are greatly looking forward to what we may find'.