A study performed by the European based GABRIEL,consortium, whose objective is to investigate the causes of asthma, has discovered new genes linked to susceptibility to disease. The authors of this study also noted that, surprisingly, the genes that control the levels of antibodies that cause allergies (immunoglobulin E or IgE) have little or no impact on the presence of asthma and, similarly, the asthma susceptibility genes have little effect on levels of immunoglobulin E. This means that allergies which accompany many cases of asthma are like to be a consequence of this disease rather than its cause. The study, which counted with the contribution of Ivo G. Gut and Simon Heath, respectively director and head of bioinformatics at the National Center for Genome Analysis (CNAG), based in the Barcelona Science Park, is published today in the New England Journal of Medicine ((DOI: N Engl J Med 2010; 363:1211-1221).

The GABRIEL consortium studied over 10,000 asthmatics and 16,000 normal subjects matched for each country of origin. In total the consortium carried out over more than half a million genetic tests on each subject, covering all genes in the human genome.

The researchers have discovered several new genes that predispose to asthma. Some of these genes are in pathways that tell the immune system when the lining of the airways (the mucosa) has been damaged. Other genes may control the rate of healing of the airways after they have been injured.

The study showed that genetic effects are weaker in adults, and that the most important gene in children (known as ORMDL3/GSDMB) does not have effects on patients who developed asthma after they had grown up.

The GABRIEL scientists found that the newly discovered genetic variants affected more than a third of children with asthma in their study, and that the genes had strong effects on cases of severe asthma. They suggested that concentrating on these genes would lead (eventually) to better therapies for the illness.The scientists found that genetic testing would be of no value in 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 are still working together to identify environmental exposures that could protect against the illness.

Professor Ivo Gut, former Deputy Director of the CEA-CNG and now Director of the CNAG said “These results constitute a huge leap forward in the understanding of asthma that will lead to major advances in the treatment and quality of life of people suffering from the disease. It has been an immense effort to get this far but is well worth it. The generous support from the funding agencies, the kind donation of DNA by the research subjects and the huge personal dedication of the collaborators of the Gabriel consortium have made this study possible.”

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