6 research outputs found
Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis
Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown
Su1953 Esophageal Strictures in Children Contain Focal Obliterative Muscularization and Mural Inflammation
High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders
Pediatric Eosinophilic Esophagitis Symptom Scores (PEESS v2.0) identify histologic and molecular correlates of the key clinical features of disease
Twin and family studies reveal strong environmental and weaker genetic cues explaining heritability of eosinophilic esophagitis
BACKGROUND: Eosinophilic esophagitis (EoE) is a chronic antigen-driven allergic inflammatory disease, likely involving the interplay of genetic and environmental factors, yet their respective contributions to heritability are unknown. OBJECTIVE: To quantify risk associated with genes and environment on familial clustering of EoE. METHODS: Family history was obtained from a hospital-based cohort of 914 EoE probands, (n=2192 first-degree “Nuclear-Family” relatives) and the new international registry of monozygotic and dizygotic twins/triplets (n=63 EoE “Twins” probands). Frequencies, recurrence risk ratios (RRRs), heritability and twin concordance were estimated. Environmental exposures were preliminarily examined. RESULTS: Analysis of the Nuclear-Family–based cohort revealed that the rate of EoE, in first-degree relatives of a proband, was 1.8% (unadjusted) and 2.3% (sex-adjusted). RRRs ranged from 10–64, depending on the family relationship, and were higher in brothers (64.0; p=0.04), fathers (42.9; p=0.004) and males (50.7; p<0.001) compared to sisters, mothers and females, respectively. Risk of EoE for other siblings was 2.4%. In the Nuclear-Families, combined gene and common environment heritability (h(gc)(2)) was 72.0±2.7% (p<0.001). In the Twins cohort, genetic heritability was 14.5±4.0% (p<0.001), and common family environment contributed 81.0±4% (p<0.001) to phenotypic variance. Proband-wise concordance in MZ co-twins was 57.9±9.5% compared to 36.4±9.3% in DZ (p=0.11). Greater birth-weight difference between twins (p=0.01), breastfeeding (p=0.15) and Fall birth season (p=0.02) were associated with twin discordance in disease status. CONCLUSIONS: EoE recurrence risk ratios are increased 10–64-fold compared with the general population. EoE in relatives is 1.8–2.4%, depending upon relationship and sex. Nuclear-Family heritability appeared to be high (72.0%). However, Twins cohort analysis revealed a powerful role for common environment (81.0%) compared with additive genetic heritability (14.5%)