Genome-Wide Meta-Analysis Provides Insight into the ‘Atopic March’

SEVEN genetic risk loci have been identified for the ‘atopic march’, the sequential progression of different allergic conditions frequently seen in those who suffer from allergies, in a recent meta-analysis. This research has provided insight into the genes responsible for the adverse disease course.

Many people who suffer from allergies typically follow a common allergy ‘career’; atopic dermatitis (eczema) during infancy tends to be the first clinical manifestation, typically followed by food allergies, asthma, and/or allergic rhinitis, with severe and persistent allergic disease manifestations being the norm. It is estimated that 20–30% of infants with eczema undergo this disease course. The progression patterns involved in the march have been a hot topic for research in recent years, as the allergic conditions can manifest in different orders. A genome-wide association study (GWAS) using information from nearly 20,000 people has now identified seven genetic risk susceptibility loci responsible for the course of disease.

The study involved a meta-analysis of 12 studies covering cases of eczema preceding asthma. All of the studies were GWAS based on millions of genetic variants called single-nucleotide polymorphisms in 2,428 patients and 17,034 healthy individuals. Seven genetic risk loci were revealed, two of which were previously unknown. The two novel loci appear to be specific for the atopic march phenotype, and are thought to predominantly influence the connection between eczema and asthma. The study also revealed that regions responsible for determining the risk of eczema appear to mainly be those that also determine the risk for further development of the typical allergic career. This suggests that eczema genes contribute significantly to the atopic march, and so the development of eczema during infancy may play an important role in onset of the unfavourable disease course.

These results have shown for the first time that specific genetic loci can influence the course of disease in the atopic march. Prof Young-Ae Lee, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, commented: “Seen from a physician’s perspective, the prominent role of atopic dermatitis genes for later-onset of asthma is very interesting. Our findings suggest that prevention or consequent therapeutic interventions in cases of paediatric atopic dermatitis may stop the further development of the atopic march.”

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