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.
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 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.

‘Very large data sets have to be examined for the genetic risk factors of allergic diseases to be identified,’ explained Professor Young-Ae Lee, a researcher at the MDC and Head of the Charité’s ECRC paediatric 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.

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.

‘The results of this study explain why some people are particularly prone to allergies,’ said 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.

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