rs1032757 (ATP6AP1L): Eosinophilic Esophagitis GWAS

Key takeaways

• rs1032757 sits near the ATP6AP1L and RPL5P16 genes and appears in a genome-wide association study (GWAS) of pediatric eosinophilic esophagitis
• Eosinophilic esophagitis (EoE) is a rare food allergy-related condition in which eosinophils (a type of white blood cell) accumulate in the esophagus, affecting roughly 1 in 10,000 people
• The study enrolled 351 pediatric cases and roughly 3,100 controls across two U.S. children's hospitals, all of European ancestry
• About 73% of EoE patients in the study had a concurrent allergic condition such as asthma, eczema, or hay fever
• Evidence for rs1032757's specific effect on EoE risk is not available from the current literature; findings should be considered preliminary

What the research says The only study on file investigated genetic susceptibility to pediatric eosinophilic esophagitis - a food allergy-related inflammatory disease defined by accumulation of eosinophils (a type of white blood cell) in the esophagus - using genome-wide genotyping of approximately 550,000 SNPs in 181 confirmed cases and 1,974 controls (discovery phase), then replicated findings in 170 cases and 1,130 controls (replication phase). EoE was estimated to carry a sibling risk ratio (λS; a measure of familial clustering that expresses how much more commonly a disease occurs in siblings of affected individuals compared with the general population) of approximately 80, far exceeding the sibling risk for related conditions such as asthma (λS ~2), indicating strong genetic heritability. The primary genome-wide significant finding in this study was rs3806932 upstream of the TSLP gene on chromosome 5q22 (odds ratio 0.54 in the discovery cohort; combined p-value 3.19 × 10^-9), not rs1032757; the provided text does not report effect-size data specific to rs1032757.

Reported associations

• Eosinophilic esophagitis (EoE): rs1032757 appears in the context of a multi-center GWAS of EoE susceptibility spanning 181 discovery-phase and 170 replication-phase pediatric cases vs. approximately 3,100 controls (all of European ancestry); the primary genome-wide significant hit reported in this study was rs3806932 at chromosome 5q22 near TSLP and WDR36 (OR = 0.54, combined p = 3.19 × 10^-9), while effect-size data for rs1032757 specifically are absent from the available text

Evidence quality The study uses a two-cohort GWAS design with discovery and independent replication phases, a robust approach for identifying common-variant associations and reducing false positives. Total case count (351) is modest, consistent with EoE's estimated incidence of approximately 1 in 10,000. All participants were of European ancestry, which limits generalizability to other populations. Genome-wide significance (combined p = 3.19 × 10^-9) was achieved for the 5q22 locus centered on TSLP; whether rs1032757 reached that threshold or any sub-threshold level of significance is not established in the provided text. No independent replication of rs1032757 itself is documented in the available literature. Evidence for this variant should be considered preliminary and incomplete pending further published studies.

Lifestyle considerations No lifestyle considerations on file for this variant.