GWAS identifies four novel eosinophilic esophagitis loci

Abstract

Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the oesophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune diseases, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the oesophagus. The identification of five EoE loci, not only expands our aetiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, oesophageal inflammation and remodelling.

Figure 1. Manhattan plot of the EoE discovery GWAS

N= 603 cases and 3637 controls. -log10 Pvals on the y-axis plotted against ascending physical position on the x-axis. The dotted red line represents the genome-wide significance threshold Pval ≥ 5×10⁻⁸

Figure 2. CAPN14 is highly expressed in the esophagus

transcriptome sequencing data from the GTEx project indicates CAPN14 is predominantly expressed in the esophageal mucosa (n= 106). Each boxplot represent a measure of CAPN14 gene expression, plotted on the y-axis for a given tissue, plotted on the x-axis. The measure of expression used is reads per kilobase million (RPKM). The boxplot whiskers represent the data range across the 106 replicates, with the notch in the box representing the median expression value.