In what researchers believe is the largest genome-wide association study ever done on the shared genetics of allergy and autoimmune diseases, scientists have identified genetic variants that influence risk for both conditions.
“To our knowledge, no previous study has had sufficient statistical power to systematically explore commonalities in the genetic architecture between allergy and autoimmunity,” wrote the study’s lead authors Hans Bisgaard and Klaus Bonnelykke, of the University of Copenhagen and the Copenhagen University Hospital.
Genetic Variants Identified
In total scientists from more than two dozen institutions, including 23andMe, participated in this research.
The findings, published in the Journal of Allergy and Clinical Immunology, come at a time when scientists are trying to explain a surge in the prevalence of both allergy and autoimmune diseases in recent decades.
The study identified 29 genetic variants associated with both allergy (to cats, dust-mites, and or pollen, or an allergic sensitization) and one of 16 different autoimmune diseases such as Crohn’s disease, multiple sclerosis and inflammatory bowel disease. In addition to finding genetic associations between these conditions, the findings may help untangle the complex relationship between allergy and autoimmunity.
Shared Biological Pathways
The study also allowed researchers to more clearly see the shared biological pathways and genetic mechanisms for allergies and autoimmune diseases. For example, many of the shared genetic variants are in or near genes associated with the immune response, regulation of T cells — the white blood cells that are essential for immunity — and regulation of cellular function.
“Our study thereby provides further understanding of the complex genetic relationship between allergy and autoimmune diseases,” authors said.
The researchers also found that while a little under half of the genetic factors increased the risk for both allergies and autoimmune disease, the remainder of the variants had opposing effects on the two conditions — raising the risk in one, while decreasing the risk in the other. The latter finding may be helpful in predicting how treating the causes of certain conditions could increase the risk of others.
Very Large Dataset
The researchers used aggregated non-identifying data from several different studies in a meta-analysis that in total had data from 62,330 people, including more than 40,000 customers from 23andMe who consented to participate in research. This very large dataset allowed researchers to efficiently see if associations for 290 genetic loci previously identified to influence the risk for more than a dozen autoimmune diseases also influence allergy risk.
According to the researchers, looking at the common genetic architecture of these conditions may also help shed more light on the environmental influences that may be contributing to the increase in the prevalence of allergies and autoimmune disease in recent times. Separate research has shown how these conditions share some of the same environmental risk factors; so, for instance, a child born through Caesarian section is at a higher risk for both allergies and autoimmune diseases. This may have to do with a change in the exposure a newborn has to microbes, which might in turn change their immune response.
Theories
There are several different theories about why this may happen.
For example some research has looked at the “hygiene hypothesis,” which posits that the cleanliness of modern society is compromising our microbiome and the good bacteria that live in and on our bodies, and in turn harming our bodies’ immune response.
This is also not the first time 23andMe has been involved in new allergy research. A study done by 23andMe and researchers at the University of Bristol’s Avon Longitudinal Study of Parents and Children (ALSPAC) in the UK — was the largest genome-wide association study at the time conducted on common allergies and found new genetic associations for asthma and allergies.
The findings in this latest study, made possible in part by 23andMe customers who consented to research, offer new insight into the shared biology of autoimmune disease and allergies, and in turn give scientists an opportunity to focus on the role of the immune response, T cell regulation, and cell function in these interrelated conditions.