UQDI Researchers Lead Largest Ever Genetic Study of Eczema: ten new genes identified

5 Nov 2015

UQDI Researchers Lead Largest Ever Genetic Study of EczemaBy Dr Marie-Jo Brion and Dr Fiona McMillan

Researchers from the University of Queensland Diamantina Institute have led an international team of researchers as part of the largest ever genetic investigation into the causes of eczema. Their research has identified ten new genes involved in the disease, revealing important new information about the role the immune system plays in its development.

Eczema is a skin condition that affects 1 in 5 Australians and is particularly common in young infants. The condition produces inflammation of the skin resulting in red, itchy and dry patches, often accompanied by weeping of fluid from the skin. Eczema can significantly affect a person’s quality of life and while in some patients can be controlled to a certain extent, there is currently no cure. A number of factors are known to aggravate eczema, such as heat, soaps and perfumes, environmental allergens and stress. However, precisely what causes a person to develop eczema in the first place is unknown..

Genome-wide association studies (GWAS) are a powerful approach that can reveal the genetic underpinnings of complex diseases such as eczema. They involve genotyping thousands of individuals on hundreds of thousands of genetic markers across their genomes. These markers, which are points in the DNA sequence that differ between individuals, are then analysed to see if they are associated with a particular disease.

A number of GWAS have been performed to help uncover genes involved in eczema, with the aim of identifying the biological mechanisms involved. This has led to the identification of a number of genes that play a role in eczema, which have lent significant support to the theory that a break down in skin barrier function contributes to the disease. Despite these advances, the number of genes discovered has been fairly limited, primarily because each study has only involved a modest number of patients and controls. In order to identify additional genes involved in eczema, studies involving much larger sample sizes are required.

The quest for a bigger, more powerful GWAS led Dr Lavinia Paternoster at the University of Bristol, together with Professor David Evans at the University of Queensland Diamantina Institute, to establish their latest research collaboration. Together, the researchers combined information from 26 studies around the world, integrating data from previous studies together with data from a range of new sources. The comprehensive GWAS ultimately involved 20,000 eczema cases and 95,000 controls, making it the largest eczema GWAS to date and one of the largest GWAS of any disease so far.

From this large new collaboration, Evans and Paternoster identified a large number of regions of the genome implicated in the development of eczema. This led to the identification of 10 new genes involved in the disease and many of these are known to be involved in autoimmunity, which is when the immune system attacks the body’s own cells and tissues. Indeed, the researchers observed a large cross-over between the genetics of eczema and the genetics of inflammatory bowel disease. According to Prof Evans, this finding was somewhat unexpected and implicates common biological causes across these disorders.

Prof Evans explains that the study also identified the involvement of a gene called Langerin, which has not been implicated in any disease previously. This gene is usually turned on in Langerhan’s cells, which are important immune cells in the skin that teach other immune cells to either attack or calm down. This finding suggests that mutations in Langerin may cause the gene to malfunction and that this may play a significant role in eczema.

The investigators emphasise that while a break down in the skin barrier is indeed an important contributor to eczema and a target for prevention and treatment, these new findings provide compelling evidence for the role of immune responses in the development of eczema and lend strong support for the idea that therapeutic approaches should also be directed at immune modulation.

Publication: Nature Genetics, October 2015

Media: Kate Templeman, k.templeman@uq.edu.au +61 7 3443 7027, +61 (0)409 916 801