title: Population-based familial aggregation of eosinophilic esophagitis suggests a genetic contribution.
abstract: BACKGROUND
  Prior familial clustering studies have observed an increased risk of eosinophilic esophagitis (EoE) mostly among first-degree relatives, suggesting a genetic contribution to EoE, and twin studies have suggested a powerful contribution from environmental factors.
  
  
  OBJECTIVE
  This study sought to clarify the contribution of genetic factors to EoE through estimation of familial aggregation and risk of EoE in extended relatives.
  
  
  METHODS
  The Utah Population Database, a population-based genealogy resource linked to electronic medical records for health care systems across the state of Utah, was used to identify EoE cases and age, sex, and birthplace-matched controls at a 5:1 ratio. Logistic regression was used to determine the odds of EoE among relatives of EoE probands compared with the odds of EoE among relatives of controls.
  
  
  RESULTS
  There were 4,423 EoE cases and 24,322 controls. The population-attributable risk of EoE was 31% (95% CI, 28% to 34%), suggesting a relatively strong genetic contribution. Risks of EoE were significantly increased among first-degree relatives (odds ratio [OR], 7.19; 95% CI, 5.65-9.14), particularly first-degree relatives of EoE cases diagnosed <18 years of age (OR, 16.3; 95% CI, 9.4-28.3); second-degree relatives (OR, 1.99; 95% CI, 1.49-2.65); and first cousins (OR, 1.35; 95% CI, 1.03-1.77), providing evidence of a genetic contribution. However, spouses of EoE probands were observed to be at increased risk of EoE (OR, 2.86; 95% CI, 1.31-6.25), suggesting either positive assortative mating or a shared environmental contribution to EoE.
  
  
  CONCLUSIONS
  This study supports a significant genetic contribution to EoE as evidenced by increased risk of EoE in distant relatives.
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, Utah. Electronic address: kristina.allen@utah.edu.
authors.forename: Kristina
authors.initials: K
authors.lastname: Allen-Brady
authors.affiliation: Department of Pediatrics, University of Utah, Salt Lake City, Utah.
authors.forename: Rafael
authors.initials: R
authors.lastname: Firszt
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: John C
authors.initials: JC
authors.lastname: Fang
authors.affiliation: Huntsman Cancer Institute Utah Population Database Resource, University of Utah, Salt Lake City, Utah.
authors.forename: Jathine
authors.initials: J
authors.lastname: Wong
authors.affiliation: Huntsman Cancer Institute Utah Population Database Resource, University of Utah, Salt Lake City, Utah.
authors.forename: Ken R
authors.initials: KR
authors.lastname: Smith
authors.affiliation: Department of Internal Medicine, University of Utah, Salt Lake City, Utah.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Peterson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D057765:Eosinophilic Esophagitis / Q000235:genetics*; D005190:Family; D005260:Female; D059647:Gene-Environment Interaction; D005789:Genealogy and Heraldry; D006801:Humans; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic; D044382:Population Groups; D012306:Risk; D014589:Utah; D055815:Young Adult
keywords: Eosinophilic esophagitis; Utah Population Database; familiality analysis; family clustering