The world's largest multi-centre study of asthma has identified five new DNA variants related to asthma, that all point towards changes in the immune system. The study has been published in Nature Genetics and according to one of the study’s authors, Professor Torben Sigsgaard from Aarhus University, it opens for new discussions about asthma treatment.

2018.05.17 | Nanna Jespersgård

The fact that such DNA changes are so evident in asthma is completely new knowledge, says professor Torben Sigsgaard.

The immune system, which consists of the organs, tissues and cells whose main task is to provide the body’s immune defences, plays an important role in the development of asthma.

This is shown by a recently published research project which, for the first time, reveals that asthma is directly linked to five specific DNA deviations which are already known to occur in connection with immune and autoimmune diseases such as rheumatoid arthritis, multiple sclerosis and Crohn's disease.

"This means that the five DNA changes that have now been mapped can be linked to a number of diseases, among them asthma. This knowledge may be important in relation to explaining why some people get asthma. In the longer term, it opens for new discussions about how we treat the disease," says Torben Sigsgaard from the Department of Public Health at Aarhus University. 

The largest asthma study in the world thus far

Professor Torben Sigsgaard is one of the many researchers behind the study 'Multiancestry association study identifies new asthma risk loci'. The article has been published in the journal Nature Genetics as a multi-centre study, where researchers pool (or if you will: recycle) the existing genetic studies of asthma in a meta-analysis, to see if any new knowledge can be extracted from the extensive amount of compiled data.

The new study is therefore a global analysis with an abundance of authors and is based on ethnically diverse populations from most parts of the world. A total of 142,000 subjects, including 24,000 asthma patients, have contributed to the new genetic discoveries.

"It is so far the largest study of asthma’s genetics in the world and the five specific DNA changes – which we as researchers term newly discovered asthma loci – are an example of what such a multi-centre study can be used for," says Torben Sigsgaard, while explaining the terminology loci (in singular form ‘locus’) as the places on a chromosome where a given gene is located.

"We have not previously been able to find these divergent genes in asthma patients, and the next obvious step is to look at these genes in other populations, that is in the asthma patients we treat and who form part of future research projects. So we can hopefully learn more about whether we can stimulate or attenuate the effects of the DNA changes, but there is still some way to go," says Torben Sigsgaard.

He explains that a correlation has previously been demonstrated between these DNA changes and other disorders that involve the immune apparatus such as inflammatory diseases including Crohn's disease and ulcerative colitis, which affect the rectum and the large intestine. However, the fact that such DNA changes are so evident in asthma is completely new knowledge. 

A mysterious illness

Asthma is a chronic lung disease caused by persistent inflammation and irritation of the airways which health professionals term inflammation. Between 250,000 and 300,000 adult Danes are diagnosed with asthma. In addition, between seven and ten per cent of all school children in Denmark suffer from asthma.

Neither medical doctors nor researchers know the cause of the disease in adults. However, it is known that the disease often begins in schoolchildren at the same time as the development of allergies.

"But inflammation is not actually allergy, and it is therefore important knowledge that DNA changes associated with asthma so clearly point towards the immune system," says Torben Sigsgaard.

More about asthma and the immune system

• Asthma is characterised by shortness of breath, coughing or wheezing.
• The symptoms are due to the respiratory mucosa overreacting by contracting strongly and producing more mucus when exposed to various factors such as cold, infections or 'irritants’ which can vary from patient to patient (e.g. smoke, perfume or cooking fumes).
• An asthma diagnosis can be made based on symptoms, the measurement of lung function and in some cases an allergy test – which often shows nothing in many adults.
• An immunodeficiency occurs when the immune system loses the ability to combat the pathogens that attack the immune system.
• Autoimmunity occurs when the immune system loses the ability to distinguish between good and bad cells, after which the body can end up 'attacking itself'.

The research results – more information 

• Type of study: Multi-centre study with a meta-analysis.
• Partners from Denmark and abroad: In addition to Professor Torben Sigsgaard and Vivi Schlünssen from Aarhus University, many researchers from around the world were involved. Hans Bisgaard and Klaus Bønnelykke from the University of Copenhagen also contributed along with Bjarke Feenstra, Frank Geller and Mads Melbye from Statens Serum Institute (SSI).
• External funding came from EU GABRIEL, read more at: http://ec.europa.eu/research/infocentre/article_en.cfm?id=/research/headlines/news/article_06_05_08_en.html&item=&artid= 
• Direct link to the abstract of the scientific article ‘Multiancestry association study identifies new asthma risk loci’ which the article is based on: DOI: 10.1038/s41588-017-0014-7 or
• https://www.nature.com/articles/s41588-017-0014-7

Contact

Professor, PhD Torben Sigsgaard
Aarhus University, Department of Public Health,  
Environment, Occupation and Health
Direct tel.: (+45) 8716 8013
Mobile: (+45) 2899 2426
Email: ts@ph.au.dk