05:06pm Monday 11 December 2017

New genes discovered that influence the risk of allergic diseases

The world’s largest study into allergies has shown that the genetic risk factors for atopic dermatitis (eczema), hay fever, and asthma are generally inherited together. The findings of this study by a consortium of researchers, including research groups from the MDC and Charité, have now been published in Nature Genetics. 

What does an allergic reaction of the skin have to do with asthma and hay fever? It is well known that allergic diseases often occur simultaneously or in succession. So are there certain genes that increase an individual’s risk of developing allergies? Or does one allergic disease trigger another?

Up to now, genetic studies have focused only on individual allergic diseases. But the SHARE study, the world’s largest study into the genetic risk factors for allergic diseases, adopted a new approach. The study, which was published in Nature Genetics and involved the participation of working groups from Berlin, focused on the three most common allergic diseases: eczema, hay fever, and asthma. The study proved that numerous genetic loci increase the risk of developing all three diseases. A total of 136 separate positions in the genome were found that are risk factors for developing the allergies, 73 of which had not previously been reported in this context.

Studying the data sets of 360,000 participants

“Very large data sets have to be examined for the genetic risk factors of allergic diseases to be identified,” says Professor Young-Ae Lee, a researcher at the MDC and head of the Charité’s ECRC pediatric allergy clinic. As a result, allergy researchers from all over the world came together to form the SHARE consortium and enable the joint analysis of data collected by all participating research groups. Unlike previous studies, all patients included in these data sets suffered either from eczema, hay fever, or asthma – or a combination of the three. The variants identified in the genomes of 180,000 patients were compared with those of 180,000 control subjects.

Different allergic diseases have shared genetic origins

A total of 136 genetic loci were identified as increasing the risk of developing one or several allergic diseases. These were, in turn, assigned to 244 possible disease genes, most of which are involved in regulating the immune system. There seems to be genetic predisposition to the overreaction of the immune system, which is a common characteristic of all allergic diseases. Whether – and if so, when – an allergy ends up developing probably depends on other genetic factors as well as environmental influences. Sixteen of the genes identified are known to exhibit DNA methylation changes, which are trigged by environmental factors and contribute to gene regulation.

New therapeutic approaches

“The results of this study explain why some people are particularly prone to allergies,” says Professor Lee. In most cases, the inherited genetic risk factors predispose the individual to all three allergic diseases – eczema, hay fever, and asthma. New targeted therapeutic approaches would therefore combat each of these diseases. Interestingly, 34 of the identified genes are already being examined as molecular targets for new drugs to treat allergies, autoimmune disorders, and cancer.

Further Information

The Max Delbrück Center for Molecular Medicine (MDC)

The Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) was founded in Berlin in 1992. It is named for the German-American physicist Max Delbrück, who was awarded the 1969 Nobel Prize in Physiology and Medicine. The MDC’s mission is to study molecular mechanisms in order to understand the origins of disease and thus be able to diagnose, prevent and fight it better and more effectively. In these efforts the MDC cooperates with the Charité – Universitätsmedizin Berlin and the Berlin Institute of Health (BIH) as well as with national partners such as the German Center for Cardiovascular Research and numerous international research institutions. More than 1,600 staff and guests from nearly 60 countries work at the MDC, just under 1,300 of them in scientific research. The MDC is funded by the German Federal Ministry of Education and Research (90 percent) and the State of Berlin (10 percent), and is a member of the Helmholtz Association of German Research Centers. www.mdc-berlin.de

 

Manuel A Ferreira et al. (2017): “Shared genetic origin of asthma, hay fever and eczema elucidates allergic disease biology.” Nature Genetics. doi:10.1038/ng.3985

 

Max Delbrück Center for Molecular Medicine in the Helmholtz Association

 


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