Multi-ancestry genetic analysis of eczema highlights relevant pathways and potential drug targets

Ashley Budu-Aggrey and Lavinia Paternoster discuss their recent paper shedding light on genetic factors in eczema and the potential implications of understanding these links better.

Atopic dermatitis or eczema is a common allergic disease that affects up to 20% of children and 10% of adults. In order to develop effective treatments it is important to understand more about the underlying causes, particularly the genetic factors, that increase people’s risk of having the condition. This is a driver for our research.

Several genome-wide association studies (GWAS) have been performed and have identified genetic regions associated with risk of eczema, including our previous GWAS within the EAGLE (Early Genetics and Lifecourse Epidemiology) consortium. In our latest paper we shared how, with the availability of new large population-based studies, we performed the largest and most comprehensive GWAS of atopic dermatitis to date. The study looked at data from 4.6 million individuals across multiple ancestry groups. It has identified additional risk loci and found evidence of some ancestry specific signals.

We identified 91 loci associated with atopic dermatitis, 32 of which were novel. Most loci were confirmed in individuals of diverse genetic ancestry (European, Japanese, Latino and/or African American populations). However, we found evidence of two loci that may be specific to individuals of Japanese ancestry. Using multi-omic data we were able to prioritise candidate causal genes at these loci. This, in turn, has highlighted the importance of immune system pathways that are relevant to eczema and uncovered drug repurposing opportunities.

Increasing knowledge

Our study contributes a significant increase in the knowledge of atopic dermatitis genetics. It has provided robust summary data for future studies. For example, the findings will help with validating the potential causal genes that were highlighted, and investigating causal relationships with Mendelian Randomization

Building on this work, we are planning downstream analyses to follow-up the candidate genes reported and identify potential drug targets as part of the BIOMAP project. We also plan to investigate the genetic architecture of atopic dermatitis in various ancestry groups more comprehensively.

We also want to investigate underlying causal mechanisms between the condition and various comorbidities in individuals of European and non-European ancestry. There is still a need for appropriate datasets for non-European individuals which will aid further analyses and the transferability of our findings to multiple ancestry groups. This could uncover new approaches for treatment or early detection, especially in populations with a greater burden of disease.

Towards new treatment opportunities

We anticipate that amongst our results will be novel treatment target opportunities for eczema. The challenge is now to take these genetic findings and more fully understand their downstream biological impact. The end goal will hopefully be better and perhaps more personalised treatments for people with eczema.

Thank you to the study co-lead, Marie Standl from Helmholtz-Munich, and also the researchers involved. Thank you also to the funders of this work, including Medical Research Council, British Skin Foundation, British Heart Foundation, Innovative Medicines Initiative, National Research Foundation and Wellcome Trust. 

Read the paper

Leave a Reply

Your email address will not be published. Required fields are marked *