More than 100 genetic risk factors that explain why some people suffer from asthma, hay fever and eczema have been identified in a major new international study. Dr Manuel Ferreira, who led the work, said this was the first study designed specifically to find genetic risk factors that are shared among the three most common allergic conditions.

This was a genome-wide association study of 360,838 individuals, tested for association with allergic disease 8,307,659 genetic variants. 180,129 cases who reported having suffered from asthma and/or hay fever and/or eczema were compared with 180,709 controls who reported not suffering from any of the diseases.

“Asthma, hay fever and eczema are allergic diseases that affect different parts of the body: the lungs, the nose and the skin. We already knew that they were similar at many levels. For example, we knew that the three diseases shared many genetic risk factors. What we didn’t know was exactly where in the genome those shared genetic risk factors were located,"

said Ferreira, from the QIMR Berghofer Medical Research Institute in Brisbane.

136 Genome Positions

The location of those factors is important, since it tells scientists specifically which genes cause allergic conditions when they are not functioning normally.

“This knowledge helps us understand why allergies develop in the first place and, potentially, gives us new clues on how they could be prevented or treated. We analysed the genomes of 360,838 people and pinpointed 136 separate positions in the genome that are risk factors for developing these conditions. If you are unlucky and inherit these genetic risk factors from your parents, it will predispose you to all three allergic conditions,"

said Ferreira. Those 136 genetic risk factors influenced whether 132 nearby genes were switched on or off.

“We think that these genes influence the risk of asthma, hay fever and eczema by affecting how the cells of the immune system work,” he said. “Importantly, we have identified several drugs that we believe could be targeted at some of these genes to treat allergies. The first step would be to test those drugs in the laboratory."

Environmental Factors

The study also examined if environmental factors might affect whether these genes are switched on or off.

“We found that this could be happening for many of the genes we identified,” Dr Ferreira said. “For example, we found one gene – called PITPNM2 – that is more likely to be switched off in people who smoke. If this gene is switched off, then the risk of developing allergies increases."

235 million people globally suffer from asthma, according to World Health Organization estimates. Over 80% of asthma deaths occurs in low and lower-middle income countries.

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

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