Allergic disease and keratoconus: A two-sample univariable and multivariable Mendelian randomization study

IF 3.9 2区医学 Q2 ALLERGY World Allergy Organization Journal Pub Date : 2024-11-22 DOI:10.1016/j.waojou.2024.100993

Hanlu Xu , Yajing Wen , Huikang Zheng , Dan Jiang , Wei Chen

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Abstract

Background

There is accumulating evidence that allergy is a risk factor for keratoconus. Nonetheless the association between allergic disease and keratoconus remains controversial. We performed a two-sample Mendelian randomization (MR) study to determine the putative causal association of 4 allergic diseases (allergic conjunctivitis, allergic asthma, allergic rhinitis and atopic dermatitis) with keratoconus.

Methods

Summary statistics were obtained from genome-wide association studies (GWAS) of allergic conjunctivitis (AC) (20,958 cases and 356,319 controls), allergic asthma (AA) (9631 cases and 210,122 controls), allergic rhinitis (AR) (11,009 cases and 359,149 controls), atopic dermatitis (AD) (13,473 cases and 336,589 controls), keratoconus (KC) (2116 cases and 24,626 controls) and 91 circulating inflammatory cytokines (n = 14,824). Two-sample univariable and multivariable MR analyses were performed. A two-step MR was then applied to determine whether systemic inflammatory cytokines mediated the effect of allergic disease on keratoconus.

Results

The causal odds ratio (OR) estimate of genetically determined KC was 1.66 (95% CI: 1.32–2.08; P < 0.001) for AC, 1.29 (95% CI: 1.10–1.51, P = 0.0014) for AA, 1.39 (95% CI: 1.15–1.68; P < 0.001) for AR and 1.30 (95% CI: 1.17–1.45, P < 0.001) for AD. Multivariable MR indicated a suggestive association between AC and KC after conditioning on other allergic diseases (OR 1.61; 95% CI: 1.10–2.34; P adjusted = 0.054). Two-step MR revealed that the effect was not mediated by systemic inflammatory cytokines.

Conclusions

Our findings provide evidence of a potential causal relationship between AC and KC. The effect of AC on KC may be mediated via other systemic inflammatory cytokines not included in the present study, or by alternative mechanisms. These findings may offer insight for prevention and intervention strategies to lower the risk of KC in patients with AC.

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过敏性疾病与角膜病：一项双样本单变量和多变量孟德尔随机研究

背景越来越多的证据表明，过敏是角膜炎的一个危险因素。然而，过敏性疾病与角膜病之间的关系仍存在争议。我们进行了一项双样本孟德尔随机化（MR）研究，以确定 4 种过敏性疾病（过敏性结膜炎、过敏性哮喘、过敏性鼻炎和特应性皮炎）与角膜炎之间的推定因果关系。方法从过敏性结膜炎（AC）（20958 个病例和 356319 个对照组）、过敏性哮喘（AA）（9631 个病例和 210122 个对照组）、过敏性鼻炎（AR）和特应性皮炎的全基因组关联研究（GWAS）中获得汇总统计数据、过敏性鼻炎（AR）（11009 个病例和 359149 个对照组）、特应性皮炎（AD）（13473 个病例和 336589 个对照组）、角膜炎（KC）（2116 个病例和 24626 个对照组）以及 91 种循环炎性细胞因子（n = 14824）。进行了双样本单变量和多变量 MR 分析。结果由基因决定的 KC 的因果几率（OR）估计值为 1.AC为1.66 (95% CI: 1.32-2.08; P < 0.001)，AA为1.29 (95% CI: 1.10-1.51, P = 0.0014)，AR为1.39 (95% CI: 1.15-1.68; P < 0.001)，AD为1.30 (95% CI: 1.17-1.45, P < 0.001)。多变量 MR 显示，在对其他过敏性疾病进行调节后，AC 与 KC 之间存在提示性关联（OR 1.61；95% CI：1.10-2.34；P 调整 = 0.054）。结论我们的研究结果为 AC 与 KC 之间的潜在因果关系提供了证据。AC 对 KC 的影响可能是通过本研究中未包括的其他全身性炎症细胞因子或其他机制介导的。这些研究结果可能有助于制定预防和干预策略，降低 AC 患者罹患 KC 的风险。

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来源期刊

World Allergy Organization Journal Immunology and Microbiology-Immunology

CiteScore

9.10

自引率

5.90%

发文量

审稿时长

9 weeks

期刊介绍： The official pubication of the World Allergy Organization, the World Allergy Organization Journal (WAOjournal) publishes original mechanistic, translational, and clinical research on the topics of allergy, asthma, anaphylaxis, and clincial immunology, as well as reviews, guidelines, and position papers that contribute to the improvement of patient care. WAOjournal publishes research on the growth of allergy prevalence within the scope of single countries, country comparisons, and practical global issues and regulations, or threats to the allergy specialty. The Journal invites the submissions of all authors interested in publishing on current global problems in allergy, asthma, anaphylaxis, and immunology. Of particular interest are the immunological consequences of climate change and the subsequent systematic transformations in food habits and their consequences for the allergy/immunology discipline.