Population-based familial aggregation of eosinophilic esophagitis suggests a genetic contribution
Population-based familial aggregation of eosinophilic esophagitis suggests a genetic contribution
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DOI：
10.1016/j.jaci.2016.12.979
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发表时间：
2017-10-01
影响因子：
14.2
通讯作者：
Peterson, Kathryn A.
中科院分区：
文献类型：
--
作者：
Allen-Brady, Kristina;Firszt, Rafael;Peterson, Kathryn A.
背景资料：以往的家族聚集性研究已经观察到嗜酸性食管炎（EoE）的风险增加，主要是在一级亲属中，这表明遗传因素对EoE的贡献，而双生子研究表明环境因素的强大贡献。目的：本研究试图通过估计家族聚集性和远亲EoE的风险来阐明遗传因素对EoE的贡献。犹他州人口数据库是一个基于人口的家谱资源，与犹他州卫生保健系统的电子病历相关联，用于以5：1的比例识别EoE病例和年龄、性别和出生地匹配的对照。采用Logistic回归分析，比较EoE先证者亲属与对照者亲属发生EoE的几率。结果：共发现EoE患者4,423例，对照者24,322例。EoE的人群归因风险为31%（95%CI，28%至34%），表明相对较强的遗传贡献。一级亲属中EoE的风险显著增加（比值比[OR]，7.19; 95%CI，5.65-9.14），尤其是诊断为< 18岁的EoE病例的一级亲属（OR，16.3; 95%CI，9.4-28.3）;二级亲属（OR，1.99; 95%CI，1.49-2.65）;和堂兄弟（OR，1.35; 95%CI，1.03-1.77），提供了遗传贡献的证据。然而，配偶的EoE先证者被观察到EoE的风险增加（OR，2.86; 95%CI，1.31-6.25），这表明无论是积极的排斥性交配或共享的环境贡献EOE.Conclusions：这项研究支持EoE的显着遗传贡献证明了EoE的远亲的风险增加。
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.