Custom SNP Chip Helps Boost Suspected Gene Associations in EoE from 3 to 13
Published October 2020 | Journal of Allergy and Clinical Immunology
A team of 18 co-authors spread across five research divisions at Cincinnati Children’s conducted a complex set of analyses that sharply expands the number of risk genes associated with eosinophilic esophagitis (EoE).
First author Leah Kottyan, PhD, Center for Autoimmune Genomics and Etiology, and senior author Marc Rothenberg, MD, PhD, director, Division of Allergy and Immunology, and colleagues conducted a meta-analysis of previous EoE gene studies to develop a custom single-nucleotide polymorphism (SNP) chip containing 956 possible risk SNPs.
The team used the chip to probe data from 627 people with EoE and 365 controls. Ultimately, the team sifted through more than 8,000 gene variants of potential influence to identify 13 genes that play significant roles, including six risk genes with effects at genome-wide significance and seven EoE risk loci with “strong suggestive significance.”
As expected, important risk genes were found to be active in esophageal tissues, but single-cell RNA sequencing also traced risk to genes active in seven other tissue types: the skin, lungs, fibroblasts, whole blood, the spleen, stomach and intestine.
As a group, all 13 of the highlighted risk genes appeared active in samples from people with EoE, while appearing minimally active in control samples. However, the genetic risk burden varied widely.
“Those with the highest decile of genetic burden had a greater than 12-fold increased risk of EoE compared with those in the lowest decile,” Kottyan says.
The results suggest that some or many of these genes might be used to calculate polygenic risk scores that could assist clinicians with earlier diagnosis and better-targeted treatments. But more study is needed.
“Polygenic risk scores will likely become more clinically useful as more genetic risk loci are identified and additional demographic, environmental, and clinical factors are included,” Rothenberg says.
