Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes.
627 cases, 365 controls
Eosinophilic esophagitis (EoE)-Custom single-nucleotide polymorphism (SNP) Chip
Meta-analysis with 2 independent EoE genome-wide association studies
Identification of replicated association and genome-wide significance at 6 loci: 2p23, 5q22, 10p14, 11q13, and 16p13; identification of 7 additional loci at suggestive significance (P < 10^(-10))
Abstract
Eosinophilic esophagitis (EoE) is an emerging, chronic, rare allergic disease associated with marked eosinophil accumulation in the esophagus. Previous genome-wide association studies have provided strong evidence for 3 genome-wide susceptibility loci. We sought to replicate known and suggestive EoE genetic risk loci and conduct a meta-analysis of previously reported data sets. An EoE-Custom single-nucleotide polymophism (SNP) Chip containing 956 candidate EoE risk single-nucleotide polymorphisms was used to genotype 627 cases and 365 controls. Statistical power was enhanced by adding 1959 external controls and performing meta-analyses with 2 independent EoE genome-wide association studies. Meta-analysis identified replicated association and genome-wide significance at 6 loci: 2p23 (2 independent genetic effects) and 5q22, 10p14, 11q13, and 16p13. Seven additional loci were identified at suggestive significance (P < 10 This study extends the genetic underpinnings of EoE, highlighting 13 genes whose genotype-dependent expression expands our etiologic understanding of EoE and provides a framework for a polygenic risk score to be validated in future studies.