In what is by far the largest genome wide association study on the common skin condition eczema, researchers led by a team at the University of Bristol in the UK, have identified new genetic variants associated with the ailment, as well as new evidence that the condition is strongly associated with some autoimmune diseases.
Eczema, also known as atopic dermatitis, is very common. By some estimates, it affects as many as one in five children and one in 30 adults. While it has been long known that genetics plays a large role in whether or not someone develops the condition, researchers are still trying to determine the genetic variants underlying eczema. This study not only identifies additional genetic contributions to the condition, but it also sheds more light on the biology behind its development.
The study — a meta analysis that pooled together a massive amount of data from researchers doing work at more than 100 institutions across the globe, including 23andMe — was meant to collect data from as many genome wide association studies on eczema as possible. The researchers were able to gather data from 26 different studies involving more than 115,000 people both with eczema and those without it. More than half of those were 23andMe customers who consented to research. The finding was replicated using data from more than 260,000 people, almost 90 percent of whom were 23andMe customers who consented to research.
The analysis involved looking at more than 15 million genetic variants in all, and from that work the researchers were able to not only identify 16 known genetic variants — 11 in Europeans and five in Japanese — but also uncover another 11 variants that were previously not known to be associated with eczema. All of the newly found variants are in genes or gene regions related to immune regulation, specifically T-cell activation. This points to a substantial genetic overlap with other inflammatory and autoimmune disease such as inflammatory bowel disease.
Previous research identified the importance of expression of filaggrin — proteins that bind keratin fibers in the skin — in the development of eczema. Variants in the filaggrin gene (FLG) can lead to something called a “barrier defect” in which the skin becomes more permeable and susceptible to eczema. Studies have shown that four variants in the FLG are present in between a quarter and one half of people with eczema. Those four known variants were again confirmed in this study.
“There is longstanding evidence that skin barrier defects and inappropriate immune responses to environmental antigens contributes to (eczema),” the authors said. “However, evidence for autoimmune mechanisms in (eczema), in particular in the context of progression to the chronic phase, has only recently emerged.”