Genetic clue to asthma causes

A “gene breakthrough could lead to new drugs for asthma”, according to the Daily Mail. The newspaper said the discovery of seven genes linked to asthma could lead to a cure for the condition within 10 years.

Genetic variations associated with asthma were discovered during a study that compared the DNA of 10,365 people with asthma and 16,110 people without the condition. The variants identified showed an association with childhood asthma and some were also associated with later-onset asthma.

Asthma is likely to be the product of both genetic and environmental factors, and this research helps build a better picture of the genetic factors that may contribute to a person’s risk of developing asthma. This may eventually lead to better ways of preventing or treating asthma, but such developments are likely to take some time.

Where did the story come from?

The study was carried out by the GABRIEL consortium, a collaboration between researchers from institutes across Europe and other countries that attempts to identify the genetic and environmental causes of asthma. The study was funded by the European Commission, the French Ministry of Research, the Wellcome Trust and Asthma UK. It was published in the peer-reviewed New England Journal of Medicine.

The research was generally covered in a balanced way by the Daily Mail , BBC News and the Daily Mirror . Although the Mail said that drugs based on the study’s findings “could be developed within 10 years”, it is difficult to know whether this is a reasonable timescale. Developing new drugs is a lengthy and unpredictable process. The Mirror suggested that the findings prove that “allergies don’t trigger asthma”. However, the findings of this study will need to be considered by experts in light of other research evidence as well as further studies designed to test this theory.

What kind of research was this?

This genome-wide association study looked for genetic variations associated with the risk of asthma. The researchers had previously conducted a smaller study to look at this topic, but the current study included over 10 times as many participants.

The type of study design used is appropriate for addressing the researchers’ question.

What did the research involve?

The researchers compared the DNA from 10,365 people with asthma (the cases) with 16,110 people without asthma (the controls). They examined the genetic sequences at over half-a-million known sites throughout the participants’ DNA to identify any genetic variants that were more or less common in people with asthma than those without it.

The participants were European or of European descent living in Canada, the US or Australia. The cases had all been diagnosed with asthma by a doctor. For some of the analyses, the participants were divided into people whose asthma had begun in childhood (before the age of 16) and those with later-onset asthma (which developed at the age of 16 or later). People who developed asthma at an unknown age, those whose asthma was related to their work (occupational asthma) and those with severe asthma were also considered separately in some analyses.

As well as looking for genetic variations associated with asthma, the researchers also looked for genetic variations associated with levels of a substance called IgE in the participants’ blood. IgE is a protein involved in allergic reactions and is produced by the immune system. Some people with asthma also have problems with allergies, and the researchers wanted to see if similar genetic variations increased the risk of raised IgE levels and asthma.

What were the basic results?

When they looked at all participants together, the researchers identified five particular genetic variations with a significant association with asthma. When looking at childhood and later-onset asthma separately, most of these genetic variations showed a greater association with childhood asthma than later-onset asthma. The individual variations each altered the risk of developing asthma by between 11% and 20%.

A set of variations on one part of chromosome 17 was associated with childhood asthma only. The two variations in this region with the strongest association with childhood asthma were within the GSDMB and GSDMA genes. The researchers did not identify any genetic variations specifically associated with occupational or severe asthma.

Only one variant near the HLA-DR gene had a statistically significant association with levels of the IgE protein in the participants’ blood. Neither this, nor any of the other variants with weaker associations with IgE levels, had an association with asthma. These analyses included 7,087 people with asthma and 7,667 controls whose IgE levels had been measured.

The researchers identified seven variations associated with the risk of childhood asthma. Using these seven variations, they could correctly identify only 35% of people who had asthma and 75% of those who did not have asthma. The seven variations were together estimated to account for 38% of cases of childhood asthma. When tested in a separate group of 517 cases and 3,486 controls, these variations accounted for 49% of the risk of developing asthma at any age.

These results suggest that testing for these variations would not be very effective at identifying an individual’s risk of asthma, although they made a considerable contribution to the risk of asthma in the community.

How did the researchers interpret the results?

The researchers concluded that some genetic factors appear to play a greater role in childhood asthma than later-onset asthma and vice versa. They say that a few common genetic variants are associated with asthma risk at all ages. The genes implicated by their findings are involved in telling the immune system that the cells covering the airways are damaged, and in inflammation of the airways. The findings also suggest that raised IgE levels play only a small role in the development of asthma.

Conclusion

This research has identified a number of genetic variations associated with the risk of asthma. There are some points worth considering when interpreting the results of this study:

• The researchers carried out some replication of their results in a separate set of cases and controls, but further replication in other samples would increase the likelihood that these variants are having an effect on asthma.
• The study only included people of European origin, so the findings may not apply to people of non-European backgrounds.
• While the genetic variations identified may themselves influence the risk of asthma, it is also possible that they are simply near other variations that affect the risk. Further research is needed to pinpoint the variants that give rise to the biological changes that result in asthma.
• Although the results suggest that IgE may not play a role in the development of asthma, these findings need to be considered by experts in light of other research evidence and studies designed to test this theory.

Diseases such as asthma are likely to have both genetic and environmental risk factors, and studies such as this help increase our understanding of what these risk factors might be. While this greater understanding may eventually lead to better ways of preventing or treating asthma, the development of drugs is a long, complicated and unpredictable process – there are no guarantees that this work will lead to new treatments, and even it eventually did it would take several years.