Unraveling the link between atopic dermatitis and autoimmune diseases in children: Insights from a large-scale cohort study with 15-year follow-up and shared gene ontology analysis

IF 6.2 2区 医学 Q1 ALLERGY Allergology International Pub Date : 2024-01-17 DOI:10.1016/j.alit.2023.12.005
Jungho Ahn , Seungyong Shin , Gi Chun Lee , Bo Eun Han , Eun Lee , Eun Kyo Ha , Jeewon Shin , Won Seok Lee , Ju Hee Kim , Man Yong Han
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Abstract

Background

Atopic dermatitis and autoimmune diseases are highly heritable conditions that may co-occur from an early age.

Methods

The primary study is a national administrative cohort study involving 499,428 children born in 2002, tracked until 2017. Atopic dermatitis was defined as five or more principal diagnoses of atopic dermatitis and two or more topical steroid prescriptions. We estimated the risks for the occurrence of 41 autoimmune diseases, controlling for risk factors. In addition, we sourced a gene library from the National Library of Medicine to conduct a comprehensive gene ontology. We used Gene Weaver to identify gene set similarity and clustering, and used GeneMania to generate a network for shared genes.

Results

Exposed and unexposed groups included 39,832 and 159,328 children, respectively. During a mean follow-up of 12 years, the exposed group had an increased risk of autoimmune disease (hazard ratio, 1.27 [95 % confidence interval, 1.23–1.32]) compared to the unexposed group. The hazard ratios of autoimmune illnesses consistently increased with two- and five years lag times and alternative atopic dermatitis definitions. Shared genes between atopic dermatitis and autoimmune diseases were associated with comorbidities such as asthma, bronchiolitis, and specific infections. Genetic interactions of these shared genes revealed clustering in Th1, Th2, Th17, and non-classifiable pathways.

Conclusions

Atopic dermatitis was significantly associated with an increased risk of subsequent autoimmune disease. we identified the genetically associated disease in atopic dermatitis patients comorbid with autoimmune disease and demonstrated a genetic network between atopic dermatitis and autoimmune diseases.

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揭示儿童特应性皮炎与自身免疫性疾病之间的联系:一项为期 15 年的大规模队列研究和共享基因本体分析的启示。
背景:特应性皮炎和自身免疫性疾病是高度遗传性疾病,可能从小就同时发生:主要研究是一项全国行政队列研究,涉及 2002 年出生的 499,428 名儿童,追踪至 2017 年。特应性皮炎的定义是五次或五次以上的特应性皮炎主要诊断和两次或两次以上的局部类固醇处方。在控制风险因素的前提下,我们估算了 41 种自身免疫性疾病的发病风险。此外,我们还从美国国家医学图书馆获取了一个基因库,以进行全面的基因本体研究。我们使用 Gene Weaver 来识别基因组的相似性和聚类,并使用 GeneMania 生成共享基因网络:暴露组和未暴露组分别包括 39 832 名和 159 328 名儿童。在平均 12 年的随访期间,与未暴露组相比,暴露组患自身免疫性疾病的风险增加(危险比为 1.27 [95 % 置信区间为 1.23-1.32])。自身免疫性疾病的危险比随着两年和五年的滞后时间以及特应性皮炎的其他定义而不断增加。特应性皮炎和自身免疫性疾病之间的共享基因与哮喘、支气管炎和特定感染等合并症有关。这些共有基因之间的遗传相互作用显示了Th1、Th2、Th17和不可分类途径的聚集:我们确定了特应性皮炎患者合并自身免疫性疾病的遗传相关疾病,并展示了特应性皮炎与自身免疫性疾病之间的遗传网络。
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来源期刊
Allergology International
Allergology International ALLERGY-IMMUNOLOGY
CiteScore
12.60
自引率
5.90%
发文量
96
审稿时长
29 weeks
期刊介绍: Allergology International is the official journal of the Japanese Society of Allergology and publishes original papers dealing with the etiology, diagnosis and treatment of allergic and related diseases. Papers may include the study of methods of controlling allergic reactions, human and animal models of hypersensitivity and other aspects of basic and applied clinical allergy in its broadest sense. The Journal aims to encourage the international exchange of results and encourages authors from all countries to submit papers in the following three categories: Original Articles, Review Articles, and Letters to the Editor.
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